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THE    ORGANS 
OF   INTERNAL   SECRETION 


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THE  ORGANS  OF 
INTERNAL  SECRETION 

THEIR  DISEASES  AND 
THERAPEUTIC  APPLICATION 

A    BOOK    FOE    GENEKAL     PRACTITIONERS 


BY 

IVO  GEIKIE  COBB,  M.D.,  M.B.C.S. 

NEUROLOGIST,    MINISTRY   OF   PENSIONS 

LATE    ASSISTANT    TO    OUT-PATIENT    PHYSICIAN,    THE    MIDDLESEX    HOSPITAL 

TEMPORARY    CAPTAIN,  R.A.M.C,  NEUROLOGIST   BRINNINQTON   SECTION 

SECOND    WESTERN    GENERAL    HOSPITAL 


THIRD  EDITION 


NEW    YORK 
WILLIAM   WOOD   &    COMPANY 

MCMXXI 


V 
Printed  in  Great  Britain 


MY  FATHER 

IN   TOKEN    OF   LOVE    AND   RESPECT 


PREFACE  TO  THIRD  EDITION 

In  this  edition  several  important  alterations  have  been 
made  in  the  construction  of  the  book.  A  chapter  has 
been  inserted  dealing  with  the  physiology  of  the 
Internal  Secretions  and  their  inter-relationships,  as  it 
has  been  felt  that  a  chapter  on  this  subject  would  be 
helpful  as  an  introduction  to  the  study  of  the  individual 
glands.  The  position  of  this  chapter  has  necessitated 
the  renumbering  of  the  subsequent  chapters;  and  two 
chapters  have  been  added  in  later  parts  of  the  book. 
Chapter  XI.  deals  with  the  inter-relationship  of  the 
ductless  glands  and  the  nervous  system,  and  forms  an 
introduction  to  the  following  chapter,  which  remains 
unchanged  from  the  Second  Edition.  Chapter  XIV. 
discusses  some  practical  points  in  hormone- therapy, 
and  continues  the  material  under  consideration  in  the 
preceding  chapter. 

Several  parts  of  the  book  have  been  largely  re- 
written, and  additions  have  been  made  in  various  places. 
The  majority  of  these  deal  with  data  which  has  recently 
been  published,  and  it  is  hoped  that  their  addition  will 
bring  the  work  thoroughly  up  to  date. 

Queen  Anne  Street,  W., 
August,  1921. 

vii 


PREFACE  TO  SECOND  EDITION 

The  fact  that  a  Second  Edition  of  this  book  has  been 
called  for  a  little  over  a  year  after  publication  appears 
to  indicate  that  it  has  fulfilled  a  want.  The  need  of 
a  small  work  dealing  with  the  Internal  Secretions  has 
apparently  been  felt,  not  only  in  this  country,  but 
in  others,  as  was  shown  by  a  demand  for  an  edition 
in  Spanish  and  another  in  Italian. 

The  entire  book  has  been  carefully  revised  and 
brought  up  to  date.  Numerous  references  have  been 
added,  and  a  chapter  dealing  with  the  Kelation  of  the 
Internal  Secretions  to  Functional  Nervous  Disease 
has  been  inserted.  The  desirability  of  a  chapter 
discussing  this  relation  had  previously  been  brought 
home  to  the  author;  but  the  large  increase  in  these 
disorders  in  the  last  year  or  two  has  made  such  an 
addition  imperative. 

Chapter  XI.  contains  a  brief  review  of  this  subject. 
Chapter  XII.  is  devoted  to  a  survey  of  the  whole 
subject,    and,    except    for    several    additions    to    the 

ix 


x  PREFACE  TO  SECOND  EDITION 

Bibliography,  remains  unchanged.  A  list  of  some 
books  dealing  with  the  subject  of  Functional  Nervous 
Disorders  has  been  added. 

The  author  desires  to  express  his  thanks  to  Dr. 
Bernard  Hart  for  much  help  in  the  classification  and 
nomenclature  of  these  disorders. 

Brinnington  War  Hospital, 
Stockport, 

September,  1918. 


PREFACE  TO  FIRST  EDITION 

This  book  is  founded  upon  articles  which  appeared 
in  the  Medical  Press  and  Circular  during  the  summer 
and  autumn  of  1916.  The  author's  object  in  writing 
these  articles  was  to  lay  before  the  busy  practitioner 
the  important  points  in  the  study  of  the  Endocrine 
Glands.  At  the  same  time  he  was  anxious  to  make 
them  as  complete  as  possible,  and  yet  keep  them 
within  the  limits  of  such  publications. 

After  the  appearance  of  these  articles,  he  received 
requests  for  reprints,  and  as  they  had  not  been  re- 
printed, and  the  interest  in  them  appeared  to  warrant 
it,  he  decided  to  publish  them  in  book  form.  The 
present  volume  comprises  these  articles,  with  slight 
alterations. 

Hormone-therapy  is  already  established  as  a  recog- 
nized therapeutic  agent,  yet  as  the  books  which  deal 
with  the  ductless  glands  and  their  secretions  are 
exhaustive  studies  including  the  results  of  laboratory 
research  in  detail,  and  require  far  more  time  to  read 
than  the  general  practitioner  has  at  his  disposal,  it 
is  difficult  for  him  to  glean  the  salient  facts  from  these 
lengthy  works.  It  seemed,  therefore,  to  the  author 
that  a  rmall  book  which  contained  an  account  of  the 

xi 


xii  PREFACE  TO  FIRST  EDITION 

diseases  and  therapeutic  application  of  extracts  of 
these  glands  might  prove  useful. 

In  publishing  this  small  volume,  however,  the 
author  wishes  to  state  that  it  makes  no  claim  to  be 
considered  an  exhaustive  and  complete  account  of 
the  endocrine  glands,  neither  can  it  be  considered  as 
a  comprehensive  therapeutic  guide  to  the  adminis- 
tration of  the  organic  extracts.  Rather  does  it  aim 
at  being  a  guide  to  other  practitioners  as  to  the  role 
which  the  ductless  glands  play  in  promoting  bodily 
health;  while  it  endeavours  to  point  out  those  morbid 
states  of  health  in  which  organic  extracts  may  be 
utilized  with  success. 

Among  the  glands  possessing  an  internal  secretion, 
the  thyroid  is  perhaps  the  one  which  has  attracted 
most  attention,  partly  on  account  of  the  well-recognized 
disorders  which  arise  in  connection  with  it,  and  partly 
because,  of  all  the  endocrine  glands,  the  thyroid 
has  been  most  utilized  therapeutically.  In  order  to 
emphasize  the  signs  and  symptoms  associated  with 
morbid  conditions  of  this  gland,  the  author  has 
devoted  three  chapters  to  the  consideration  of  Ex- 
ophthalmic Goitre  and  Thyroid  Deficiency.  The  last 
of  these  three  chapters  contains  references  to  the 
administration  of  thyroid  extract;  while  this  subject 
is  again  referred  to  in  Chapter  X. 

A  chapter  has  been  devoted  to  the  Pituitary  Gland, 
and  the  subject  of  pituitary -therapy  has  been  briefly 
reviewed.  In  Chapter  VI.  the  Adrenal  Glands  are 
described,  and  the  clinical  conditions  of  hyperadrenia 


PREFACE  TO  FIRST  EDITION  xiii 

and  hypoadrenia  are  discussed.  Chapter  VII.  deals 
with  the  Pancreas,  and  describes  its  structure,  physio- 
logical functions,  and  relation  to  glycosuria,  and 
concludes  by  referring  to  the  therapeutic  possibilities 
of  preparations  of  this  gland. 

The  subject  of  the  Internal  Secretions  of  the  Sexual 
Organs,  dealt  with  in  Chapter  VIII.,  has  been  com- 
pressed into  as  small  a  space  as  was  possible;  a  full 
account  would  have  filled  a  large  volume.  Neverthe- 
less, this  chapter  reviews  the  outstanding  features, 
suggests  ways  of  administering  extracts  of  the  genital 
glands,  and  describes  morbid  conditions  in  which  they 
may  be  helpful. 

The  Internal  Secretions  of  Digestion  form  the 
subject  of  Chapter  IX.;  and  here  the  author  has 
endeavoured  to  lay  emphasis  upon  the  therapeutic 
aspect,  as  he  believes  that  in  the  near  future  this 
branch  of  organo-therapy  will  find  a  very  wide  field 
of  utility,  and  will  succeed  in  alleviating  many  morbid 
conditions  which  have  hitherto  proved  resistant  to 
treatment. 

The  Therapeutic  Application  of  Hormones  is  sum- 
marized in  Chapter  X.  This  chapter  has  been  enlarged 
since  its  appearance  in  the  Medical  Press  and  Circular, 
and  it  endeavours  to  epitomize  the  subject  for  those 
readers  who  are  mainly  concerned  with  the  therapeutic 
aspect  of  this  subject.  It  necessarily  summarizes  the 
conclusion  of  each  chapter,  but  in  addition  references 
will  be  found  to  preparations  and  doses  not  included 
in  the  previous  chapters. 


xiv  PREFACE  TO  FIRST  EDITION 

Chapter  XI.  is  devoted  to  a  survey  of  the  whole 
subject,  and  deals  with  the  present  position  of  hormone- 
therapy. 

As  the  therapeutic  aspect  of  this  subject  was  dealt 
with  at  the  end  of  each  article,  it  has  been  decided 
to  leave  this  arrangement  unaltered.  Likewise,  the 
references  have  been  left  in  their  original  positions; 
but  a  bibliography  has  been  included  at  the  end  of 
Chapter  XI.,  so  that  those  desirous  of  a  fuller  account 
of  the  ductless  glands  and  organo-therapy  will  be  able 
to  refer  to  the  works  enumerated  there. 

In  conclusion,  the  author  desires  to  thank  the  editor 

and  proprietors   of   the   Medical  Press  and  Circular 

for   permission   to   reproduce  these  articles  in   book 

form. 

IVO  GEIKIE  COBB. 

Seymour  Street,  W., 
November,  1916. 


CONTENTS 


PAGE 

PREFACE   TO   THIRD    EDITION     -                 -                -                -  vii 

PREFACE   TO   SECOND    EDITION                   -                 -                 -  ix 

PREFACE   TO   FIRST   EDITION     -                 -                -                 -  xi 

CHAPTER 

INTRODUCTION                   -                 -                 -                 -  I 

I.    THE   PHYSIOLOGY    OF   THE   INTERNAL   SECRETIONS         -  IT 

II.    THE   THYROID   AND   PARATHYROID   GLANDS       -  38 

HI.    EXOPHTHALMIC   GOITRE                -                 -                 -  55 

IV.    THYROID   DEFICIENCY  -                 -                 -                 -  87 

v.  thyroid  deficiency  (continued)        •            -             -  103 

VI.    THE    PITUITARY    BODY                    -                 -                 -                 -  123 
VH.    THE   ADRENAL   GLANDS                  -                 -                 -                 -  151 
vm.    THE   PANCREAS                                     -                  -                  -                 -  174 
IX.    THE    SEXUAL    ORGANS    AND    THEIR    INTERNAL    SECRE- 
TIONS               ......  190 

X.    THE   INTERNAL   SECRETIONS    OF   DIGESTION       -                 -  211 
XI.    THE   INTER-RELATIONSHIP   OF   THE   DUCTLESS   GLANDS 

AND   THE   NERVOUS   SYSTEM                  -                 -                 -  232 

XH.    THE   ENDOCRINE   GLANDS   AND   NERVOUS   DISORDERS  -  244 

XLn.    THE   THERAPEUTIC   APPLICATION   OF   HORMONES              -  280 

XIV.    PRACTICAL   POINTS   IN    HORMONE-THERAPY        -                -  315 

XV.    CONCLUSIONS   AND   BIBLIOGRAPHY          -                 -                 -  331 

INDEX  --..---  343 


XV 


THE  ORGANS  OF  INTERNAL 
SECRETION 

INTRODUCTION 

The  place  which  those  glands  possessing  internal 
secretions  now  occupy  in  the  practice  of  medicine 
cannot  be  over-estimated.  Although  it  is  only  in 
recent  years  that  their  importance  has  been  under- 
stood, every  day  brings  to  our  knowledge  fresh  evidence 
of  their  vital  influences  upon  the  general  bodily  and 
mental  health.  When  it  was  discovered  that  ex- 
ophthalmic goitre  is  always  associated  with  over- action 
and  hypersecretion  of  the  thyroid  gland,  the  first  mile- 
stone had  been  passed  in  the  path  which  led  us  to  the 
discovery  of  the  important  part  which  the  hormones 
play  in  our  lives. 

What  we  may  call  the  grosser  lesions  due  to  disturb- 
ances in  the  normal  ratio  between  the  various  internal 
secretory  glands  are  nowadays  matters  of  almost 
popular  knowledge.  What  we  desire  to  emphasize 
in  this  book  are  the  smaller  sign?  and  symptoms 
which,  to  the  eye  tiained  to  observe,  show  minor 
disturbances,  either  of  one  or  more  glands  or  of  the 

1 


2    THE  OKGANS  OF  INTEENAL  SECEETION 

balance  between  these  glands.  Many  of  these  details, 
trifling  in  themselves,  have  been  proved  to  be  suffi- 
ciently characteristic  to  justify  medical  science  in  in- 
cluding them  among  the  constant  features  which  owe 
their  origin  to  the  ductless  glands.  When  the  pioneer 
work  was  being  done  on  this  subject,  the  evidences 
of  the  slighter  disturbances  of  the  endocrine  glands 
were  regarded  by  many  observers  as  too  fanciful  to 
merit  serious  consideration.  Thus,  when  Levi  and 
Kothschild  first  pointed  to  the  "  eyebrow  "  sign  as 
indicative  of  deficient  thyroidism,  it  was  hard  for  many 
students  of  these  subjects  to  convince  themselves  that 
this  sign  was  of  any  value  whatsoever. 

Nevertheless,  this  and  other  manifestations  of 
equally  slight  nature  are  now  admitted  to  be  of  the 
greatest  value  in  diagnosing  deficient  thyroid  secretion. 
Many  of  the  signs  of  kindred  nature  are  so  slender 
as  to  require  the  most  minute  study  and  the  most 
careful  observation  before  we  can  say,  with  any  degree 
of  probability,  which  particular  gland  is  at  fault. 
The  importance  of  this  lies  in  the  fact  that  many  cases 
of  "  functional  disturbances,"  which  we  have  been 
content  previously  to  cosset  with  various  preparations, 
and  to  class  as  neurotic  or  neurasthenic  according 
to  the  depths  of  our  ignorance,  are  now  recognized 
as  originating  in  abnormal  functioning  of  the  endo- 
crinic  glands.  This  much  is  now  generally  known  and 
universally  admitted.  Only  relatively  few  observers 
recognize  that  this  is  not  the  fons  et  origo  mali,  but 
only  one  stage  on  the  journey. 


INTRODUCTION  3 

The  prevalence  of  infections  of  various  kinds,  and 
the  frequency  with  which  an  individual  living  under 
modern  conditions  succumbs  to  a  "  chill  "  or  other 
disorder  not  definitely  diagnosed,  are  factors  which 
have  to  be  reckoned  with  when  considering  the  etiology 
of  endocrinic  disturbances.  The  part  which  mental 
strain  plays  in  upsetting  the  bodily  harmony  has  been 
proved  beyond  doubt  by  the  war.  There  were  count- 
less examples  of  hyperthyroidism  or  hyperadrenia  (to 
mention  the  types  most  easily  recognizable)  met  with 
supervening  upon  psychical  trauma.  These  were  cases 
which  had  been  submitted  to  sudden  and  violent 
mental  shock,  in  many  instances  supervening  upon 
previous  prolonged  mental  strain. 

It  is  justifiable  to  assume  that  the  strain  inseparable 
from  modern  civilian  life  is  likewise  able  to  produce 
endocrine  disturbance,  although  the  cause  is  usually 
of  longer  standing.  Many  patients  suffering  from  the 
neuroses,  as  well  as  certain  vague  metabolic  disturb- 
ances, are  now  beginning  to  sort  themselves  into  cate- 
gories quite  different  from  those  previously  recognized. 

To  take  a  concrete  instance,  let  us  suppose  that  a 
patient  exhibits  signs  that  the  thyroid  is  not  function- 
ing adequately.  The  patient  exhibits  many  of  the 
well-known  signs  pointing  to  this  deficiency.  Most 
of  us  are  well  content  to  leave  it  at  that,  and  even  to 
spend  time  (which  should  be  occupied  in  delving  still 
farther  and  asking  ourselves  why  such  a  deficiency 
is  present)  on  self-adulation  at  our  extraordinary 
deductive  powers.    It  is  certainly  true  that  we  can 


4    THE  OEGANS  OF  INTERNAL  SECRETION 

benefit  our  patients  by  the  exhibition  of  one  or  other 
of  the  organo-therapeutic  products,  but  we  shall  do 
so  to  a  much  larger  extent  if  we  realize  one  or  two 
simple  facts. 

When  advising  a  patient  to  take,  let  us  say,  thyroid 
extract  for  a  time,  we  are  constantly  asked  by  the 
patient  the  rationale  of  such  a  prescription.  Having 
explained  that  we  have  reason  to  believe  that  this 
gland  is  not  supplying  an  adequate  amount  of  secretion, 
on  more  than  one  occasion  we  have  been  asked  by 
the  logical  patient,  "  Have  I  got  to  continue  this 
medicine  for  the  rest  of  my  life  ?"  or,  "  Will  the  need 
for  its  administration  be  overcome  in  due  time  ?" 
This  is  an  important  matter,  because  it  makes  us 
think  for  ourselves,  and  not  blindly  prescribe  drugs 
for  indefinite  times  without  reasoning  as  to  their 
method  and  length  of  administration. 

I  think  that  we  are  justified  in  considering  for  a  few 
moments  what  underlies  the  deficiency  in  secretion. 
It  is  highly  improbable  that  one  or  other  of  the  endo- 
crinic  glands  would  suddenly  and  without  any  stimulus 
refrain  from  supplying,  or  determine  to  over-supply, 
its  valuable  contents  to  the  blood-stream.  It  is  much 
more  probable  that  some  cause,  be  it  mental  or  bodily, 
has  determined  this  upset,  and  it  behoves  us  to  realize 
that  this  is  the  case,  and  not  to  consider  our  diagnosis 
completed  when  we  have  made  up  our  mind  that  such 
and  such  a  gland  is  defective  or  over-active. 

In  his  book  on  "  Intestinal  Stasis,"  Lane  states 
that  one  of  the  effects  of  intestinal  intoxication  is 


INTRODUCTION  5 

atrophy  of  the  thyroid.  Here  we  have  a  definite 
attempt  to  go  to  the  root  of  the  trouble,  and  evidence 
is  accumulating  to  show  that  endocrine  disturbances 
are  frequently  associated  with  alimentary  toxaemia. 
For  the  present,  at  any  rate,  let  us  assume  that  this 
is  one  of  the  causes  which  underlie  submyxcedema. 
What  others  may  there  possibly  be  ?  Among  the 
causes  of  diabetes  which  find  their  place  in  most 
current  textbooks  on  medicine  is  worry  and  anxiety. 
Now,  this  is  at  once  assuming  that  mental  causes 
may  upset  a  bodily  function  or  functions,  and 
thereby  disorganize  metabolism.  And  the  writer 
would  be  the  last  to  wish  to  deny  this.  If,  there- 
fore, we  may  assent  to  this  detail  of  etiology  with 
regard  to  diabetes,  why  should  we  not  include  such 
a  cause  when  we  are  discussing  disorganization  of 
the  endocrinic  glands  ?  Many  cases  which  we  can 
call  to  mind  at  the  moment  afford  us  the  strongest 
possible  support  for  such  a  theory.  Prolonged  anxiety, 
business  worry,  a  sudden  shock,  are  said  to  be  capable 
of  producing  diabetes,  just  as  puncture  of  the  floor 
of  the  fourth  ventricle  is,  experimentally,  capable 
of  doing  the  same.  It  would  seem  at  least  equally 
probable  that  the  same  causes  can,  and  do,  upset  the 
mechanism  which  governs  the  balance  between  the 
ductless  glands. 

In  the  severe  cases  of  this  nature  (e.g.,  Graves' 
disease),  this  fact  is  sufficiently  recognized.  But  is 
it,  has  it  been,  when  we  come  to  consider  slighter 
derangements    of   these   important    glands  ?      It   is 


6    THE  ORGANS  OF  INTERNAL  SECRETION 

obvious  that  the  entire  study  of  this  subject  is  of  too 
recent  a  date  to  have  made  the  minute  clinical  study 
of  the  ultimate  cause  a  feasible  proposition.  Never- 
theless, we  now  come  to  the  time  when  our  patients 
ask  us  the  why  and  the  wherefore  of  such  prescribing. 

We  have  suggested  two  possible  causes  which  may 
underlie  the  disorganization  of  the  endocrinic  system — 
namely,  intestinal  toxaemia  (as  suggested  by  Lane); 
and  mental  causes,  such  as  worry,  anxiety,  and  mental 
strain  of  any  kind.  But  are  these  the  sole  causes 
which  may  be  held  responsible  ?  We  are  all  familiar 
with  the  damaged  health  which  may  result  from  a  long 
illness,  or,  alternatively,  from  a  sudden  short  attack, 
such  as  influenza.  The  patient  recovers  but  slowly, 
the  strength  returns  not,  the  mind  is  clouded,  and  in 
countless  other  ways  the  individual  shows  the  effects 
of  the  illness.  Hitherto  we  have  referred  to  such 
cases  as  post-influenzal  debility,  when  this  disease 
has  been  at  the  root  of  the  trouble;  or  as  "neuras- 
thenia," when  we  could  not  find  a  cause  even  as 
tangible  as  influenza.  Our  remedies  have  been 
confined,  certainly  in  many  instances,  to  a  change 
to  the  sea  or  spa,  and  a  generous  addition  to  the  diet. 
But  we  have  rarely  asked  ourselves  what  factor  under- 
lies these  "  delayed  recoveries." 

Why  should  not  the  toxins  of  influenza,  in  like 
manner  to  the  toxins  generated  by  the  inhabitants 
of  the  bowel,  or  the  adverse  mental  influences  which 
exert  their  harmful  action  where  mental  strain  is 
present,  be  capable  of  producing  an  endocrinic  dis- 


INTKODUCTION  7 

organization  ?  Hypothetically,  at  any  rate,  such  an 
occurrence  is  at  least  probable,  and  it  would  give  us  a 
reason  for  the  sudden  or  gradual  withdrawal  of  the 
internal  secretion  which  happens  to  be  deficient  in  the 
particular  case.* 

From  the  practical  standpoint,  moreover,  we  must 
advance  some  such  hypothesis  as  this  in  order  to  ac- 
count for  the  train  of  symptoms,  which,  certainly 
in  many  cases,  owes  its  origin  to  a  disturbance  of  the 
normal  ratio  which  exists  in  health  between  the  various 
endocrinic  glands.  Again,  most  of  us  are  familiar  with 
the  cases  of  delayed  convalescence  following  an 
operation.  The  patient  invariably  presents  a  similar 
picture  to  that  designated  "  post-influenzal  debility." 
In  theory,  at  any  rate,  he  ought  to  respond  to  the 
administration  of  one  or  other  of  the  preparations  of 
the  hormones,  and  in  many  cases  he  does. 

On  more  than  one  occasion  I  have  had  the  oppor- 
tunity of  putting  this  theory  into  practice.  One 
lady  consulted  me  some  years  ago  for  neurasthenia 
following  a  severe  abdominal  operation.  This  condi- 
tion had  resisted  a  wealth  of  treatment;  many  and 
diverse  remedies  had  been  tried  without  relief.  I 
hoped  that  I  might  be  enabled  to  afford  relief  by  the 
administration  of  an  organo-therapeutic  preparation. 
On  considering  her  syndrome,  I  came  to  the  conclusion 

*  It  has  recently  been  reported  in  the  Archives  of  Inter- 
national Medicine,  that  a  series  of  experiments  have  led  some 
American  investigators  to  the  belief  that  progressive  muscular 
dystrophy  may  originate  in  a  disturbed  functioning  of  the 
endocrine  glands. 


8     THE  OEGANS  OF  INTEENAL  SECEETION 

that  she  might  derive  benefit  from  the  exhibition  of 
pituitary  extract.  In  spite  of  the  laboratory  evidence, 
which  should  convince  us  that  it  is  useless  to  give  an 
extract  of  this  gland  by  the  mouth,  I  took  my  courage 
in  both  hands  and  prescribed  it.  The  result  surpassed 
even  my  optimistic  expectations.  The  lady  recovered 
her  strength  and  health;  her  digestion  righted  itself; 
her  functions  became  normal,  and  she  regained  perfect 
health.  This  result  is  striking,  for  it  followed  many 
other  remedies,  and  the  patient  herself  always  refers 
to  this  medicine  as  the  "  magic  mixture." 

I  mention  this  case  as  it  exemplifies  our  hypothesis 
that  many  and  diverse  causes  may  produce  a  change 
in  the  normal  functioning  of  these  glands.  Whether, 
in  this  particular  case,  it  was  the  shock  of  the  operation, 
the  anaesthetic,  or  the  changes  in  diet  necessitated 
by  these  procedures,  it  is  impossible  to  say.  An 
example  of  a  similar  attack  of  "  thyroid  deficiency  " 
is  the  case  of  a  lady  who,  having  nursed  her  husband 
through  a  long  and  trying  illness,  which  resulted 
fatally,  consulted  me  for  symptoms  which,  upon 
investigation,  were  shown  to  be  due  to  deficient 
thyroid  secretion.  Upon  the  administration  of  thyroid 
extract,  she  made  a  capital  recovery  and  was  restored 
to  health.* 

*  The  field  of  utility  of  thyroid  extract  is  widening  rapidly 
as  fresh  knowledge  is  gained  as  to  the  various  diseases  in  which 
disturbance  of  the  thyroid  plays  a  part.  As  an  example,  its 
action  as  a  diuretic,  and  the  use  to  which  this  can  be  put  in 
metabolic  disorders,  has  earned  for  it  the  name  "  physiological 
digitalis." 


INTEODUCTION  9 

These  cases  both  help  us  to  answer  the  question  so 
often  put  to  us  when  we  recommend  an  extract  of 
one  or  other  of  these  ductless  glands.  It  would  seem 
that,  certainly  in  many  instances,  the  administration 
of  the  extract  either  by  the  mouth  or  hypodermically 
serves  to  act  as  a  stimulus  to  the  normal  secretion, 
so  that  it  is  unnecessary  to  continue  artificially  its 
administration  for  lengthy  periods.  And,  again,  the 
prescribing  of  the  requisite  extract  at  the  right  time 
is  the  "  shortest  cut  "  to  health  which  exists. 

It  is  even  possible  that  many  of  the  benefits  which 
we  all  recognize  to  accrue  from  a  change  of  climate, 
from  a  course  of  spa  treatment,  or  from  a  sea-voyage, 
are  really  largely  efficacious  because  they  stimulate 
into  activity  the  gland  (or  glands)  which  has  been 
temporarily  inhibited  by  the  illness,  operation,  or  other 
cause.  In  this  connection  reference  may  be  made  to 
another  instance  where  "  post-influenzal  debility " 
has  yielded  to  organo-therapy.  A  lady  consulted 
me  for  this  condition,  which  had  been  in  existence 
for  five  years,  and  which  had  resisted  all  treatment. 
It  had  commenced  after  a  bad  attack  of  influenza 
five  years  before.  Her  condition  was  much  improved 
from  the  first  by  the  administration  of  thyroid  extract, 
and  she  made  a  most  satisfactory  recovery. 

The  point  which  seems  to  need  emphasizing  is  this: 
that  prolonged  illness,  shock,  mental  anxiety,  and 
many  other  causes,  produce  effects  which  owe  their 
origin  to  a  disturbance  of  the  relation  between  the 
hormones.     The  indications  are  rarely  broad.     Some- 


10    THE  OBGANS  OF  INTEENAL  SECEETION 

times  they  require  the  eye  of  a  medical  "  detective  ': 
before  their  significance  is  realized.  But  the  signs  and 
symptoms  are  rarely  wanting  if  they  are  looked  for. 

Neurasthenia  has  been  likened  to  influenza  (inas- 
much as  any  intangible  condition  has  received  this 
label),  and  has  been  dubbed  the  "  dustbin  of  the 
neurologist."  Nevertheless  it  is  a  real  and  concrete 
disease — concrete  in  the  sense  that  it  is  not  a  hotch- 
potch of  other  diseases.  Doubtless  some  of  the 
diagnoses  which  have  been  made  under  this  name 
would  in  reality  have  received  another  title  did  we 
but  realize  what  was  the  underlying  pathology. 
Some  patients  who  have  been  called  neurasthenics 
are  in  reality  neurasthenics,  but  they  are  neurasthenics 
because  they  are  suffering  from  a  deficiency  of  hor- 
mones. 

I  may  perhaps  be  allowed  to  mention  one  other 
case  as  illustrating  the  relation  between  neurasthenia 
and  the  endocrinic  glands.  During  the  course  of 
last  year  I  was  consulted  by  a  doctor  who  informed 
me  that  he  was  a  neurasthenic,  and  brought  me  a 
typewritten  account  of  his  symptoms,  in  support  of 
this  statement.  I  need  not  describe  the  case  in  detail, 
as  the  few  points  I  mention  will  serve  our  purpose. 

The  patient  complained  that  he  was  slow  mentally, 
became  extremely  tired  after  comparatively  small 
exertion,  was  exhausted  after  sexual  connection, 
unable  to  concentrate  for  any  length  of  time,  and  so 
on.  On  examination,  I  discovered  a  very  slow  pulse 
(barely  fifty  to  the  minute),  a  dry  and  rough  skin, 


INTEODUCTION  11 

prematurely  grey  hair,  especially  over  the  temples 
(the  patient  was  in  the  thirties),  trophic  changes  in 
the  skin  appendages,  and  many  other  minor  signs 
which  I  will  not  waste  time  by  enumerating.  Suffice 
it  to  say  that  the  patient  presented  a  typical  picture 
of  submyxcedema,  and  I  advised  small  doses  of  thyroid. 
Some  months  later  he  advised  me  that  he  had  suffered 
from  some  "  extraordinary  sinking  feelings  "  when  he 
had  taken  the  thyroid,  and  in  consequence  had  been 
forced  to  abandon  it.  I  explained  that  these  were 
most  certainly  due  to  the  stimulating  effect  which 
the  thyroid  would  produce  upon  the  circulation,  and 
I  encouraged  him  to  persevere  with  it.  The  interest 
of  this  case  lies  in  the  fact  that  all  the  symptoms  had 
gradually  supervened  after  an  attack  of  influenza,  and 
that  their  real  nature  had  never  been  diagnosed. 

Such  a  case  as  this  will  serve  to  show  how  a  certain 
proportion  of  patients  who  have  been  treated,  and 
only  too  frequently  dismissed  as  incurable  under  some 
such  name  as  neurasthenia,  may  be  helped  by  the 
judicious  administration  of  these  extracts. 

I  need  not  offer  an  account  of  the  symptoms  which 
make  up  these  diseases,  nor  is  there  need  for  me  to 
describe  in  detail  what  is  so  well  known  about  indi- 
vidual symptoms  of  deficiency  in  thyroid,  in  pituitary, 
or  in  adrenals.  But  one  or  two  points  have  come  to 
my  notice  about  these  conditions  that  I  should  like 
to  mention  in  passing. 

There  can  be  little  doubt  that  deficiency  in  thyroid 
secretion  comes  on  more   or  less    suddenly  in  some 


12    THE  OEGANS  OF  INTERNAL  SECRETION 

cases.  I  recall  the  case  of  a  young  male  subject  who 
developed  this  complaint  after  a  hazardous  season 
on  the  Stock  Exchange.  His  condition,  when  he 
came  under  my  observation,  was  typical,  and  he  made 
speedy  progress  under  thyroid  medication.  Again,  I 
have  seen  a  typical  attack  of  submyxcedema  develop 
after  one  of  the  exanthemata;  likewise  excessive 
thyroid  secretion  ensues  after  such  a  disease  as  rheu- 
matism. 

It  may  be  of  interest  to  note  at  this  place  the 
extraordinary  intolerance  to  tobacco  which  develops 
when  the  thyroid  secretion  is  deficient.  I  have  on 
several  occasions  observed  that  the  patient,  a  heavy 
smoker  previously,  has  had  to  abandon  the  fragrant 
weed  at  or  about  the  time  when  his  illness  commenced. 
I  have  been  told  that  even  one  cigarette  is  followed 
by  unpleasant  sensations,  and  I  have  ascertained  that 
the  blood- pressure  has  been  lowered  as  much  as  ten 
points  after  one  cigarette. 

These  occurrences  all  point  to  the  fact  that,  given 
suitable  conditions,  it  is  not  a  difficult  matter  to  upset 
the  normal  ratio  between  the  various  hormones.  It 
is  necessary  in  these  cases  to  study  the  antecedent 
conditions  with  as  much  care  as  we  should  when  taking 
the  previous  history  of,  let  us  say,  a  case  of  tuber- 
culosis. For  in  these  patients  we  can  often  discover 
some  occurrence  which  may  well  have  some  bearing 
upon  the  etiology,  and  may  give  us  valuable  informa- 
tion both  as  to  the  actual  cause  and  as  to  the  particular 
gland  at  fault. 


INTRODUCTION  13 

Unfortunately,  the  therapeutics  of  the  other  glands 
are  scarcely  in  such  a  satisfactory  state  as  that  of 
the  thyroid  gland,  and  we  do  not,  in  practice,  obtain 
results  as  striking  as  those  which  so  often  ensue  from 
the  administration  of  thyroid.  But,  before  leaving 
the  subject,  we  may  say  a  few  words  as  to  the  pre- 
scribing of  the  adrenals. 

The  extract  of  the  adrenals  may  be  given  in  the 
form  of  dry  extract,  and  it  is  often  of  great  benefit 
to  those  patients  who  are  weakly,  debilitated,  with 
a  low  blood-pressure  and  constant  fatigue.  These 
are  the  cases  of  neurasthenia  in  which  this  extract 
should  be  tried.  Again,  the  preparations  of  one  or 
other  part  of  the  pituitary  gland  are  in  some  of  these 
cases  more  beneficial;  while  it  is  sometimes  of  service 
to  use  what  Leonard  Williams  calls  a  "  mitrailleuse  ,: 
— i.e.,  a  preparation  containing  the  extracts  of  many 
glands.  Such  a  one  is  Hormotone,  and  it  is  claimed 
that  its  exhibition  is  followed  by  marked  benefit  in 
many  indefinite  conditions. 

The  method  of  treating  disease  by  means  of  extracts 
of  the  endo crinic  glands  is,  relatively,  still  in  its  infancy, 
so  we  must  not  be  hypercritical  at  that  part  of  this 
medication  which  works  without  the  support  of  the 
laboratory.  But,  as  has  been  admitted  elsewhere 
by  a  physiological  chemist,  clinical  experience  often 
is  at  variance  with  laboratory  results,  and  clinical 
results  are  not  always  in  the  wrong.  However  much 
we  may  condemn  the  indiscriminate  and  speculative 
use  of  these  extracts  without  adequate  reasoning,  if 


14    THE  OEGANS  OF  INTEENAL  SECEETION 

we  abide  by  laboratory  results,  and  never  test  these 
by  practical  endeavour,  we  are  liable  to  remain  with 
little  added  knowledge  on  these  subjects  as  the  years 
roll  on. 

The  practitioner  must  perforce  use  his  eyes  before 
he  prescribes  thyroid  extract;  he  must  be  familiar  with 
the  small  signs  which  go  to  make  up  the  picture  of 
deficient  or  excessive  action  of  this  gland ;  and  he  must 
not  hesitate  to  prescribe  this  substance,  although  the 
signs  are  slight.  He  must  be  familiar  with  the 
diagnostic  features,  and  he  must  be  equally  au  fait 
with  what  is  now  known  about  treatment.  He  must 
choose  a  carefully  standardized  preparation;  be  careful 
that  his  preparation  is  new,  and  not  several  months 
older  than  when  the  local  chemist  purchased  it  from 
the  wholesale  house;  and,  finally,  he  must  understand 
that  the  dose  is  a  matter  deserving  the  closest  atten- 
tion. Thyroid,  to  quote  one  example,  is  not  a  drug 
to  use  from  3  to  10  grains,  but  in  fractions  of  a  grain — 
certainly  to  commence  with.  Had  it  not  been  for 
the  fact  that  it  has  been  utilized  to  reduce  weight, 
the  probability  is  that  it  would  not  have  obtained  that 
popularity  which  it  now  possesses  in  the  lay  mind. 
This  has  made  its  administration  a  matter  of  danger, 
especially  when  we  consider  that  the  dose,  or  rather 
the  initial  dose,  is  often  far  too  large. 

Convalescence  is  frequently  accompanied  by  defici- 
ency in  the  thyroid  gland,  and  its  administration  in 
minimal  doses  is  of  very  real  help.  During  the  months 
which  follow  a  serious  illness,  such  as  pneumonia, 


INTRODUCTION  15 

the  administration  of  a  "  mitrailleuse  "  is  frequently 
indicated.  The  tendency  to  obesity,  or  alternatively 
to  undue  loss  of  flesh,  which  is  usual  after  severe  ill- 
nesses, would  point  to  an  upset  in  the  hormone  balance ; 
and  this  may  be  remedied  by  a  careful  study  of  the 
symptom-complex  and  the  prescription  of  a  suitable 
organo-therapeutic  extract. 

To  all  those  who  treat  neurasthenia,  who  have  to 
lighten  the  lot  of  those  unfortunate  sufferers  from  what 
are  known  as  "  the  functional  neuroses,"  the  impor- 
tance of  organo-therapy  cannot  well  be  over-estimated. 
When  administered  with  intelligence,  with  the  patient 
under  observation,  there  need  be  no  risk  in  such 
prescribing.  Rather  is  there  a  risk  in  prolonging  a 
morbid  condition  owing  to  neglect  in  the  faculty  of 
observation  or  an  oversight  as  to  the  underlying 
causation. 

Again,  what  a  difficult  matter  it  is  to  "  fatten  up  " 
some  patients.  Rest  cures,  hyperalimentation,  malt 
extracts,  digestive  ferments — all  seem  to  be  of  no 
avail.  But  the  extracts  of  the  ductless  glands  will 
often  be  found  of  service,  when  taken  with  regularity. 
It  should,  however,  be  remembered  that  thyroid 
must  be  prescribed  with  great  care  in  such  cases  as 
these.  Extracts  of  the  brain  and  spinal  cord,  of  the 
pancreas  and  liver,  of  the  testes  and  seminal  vesicles, 
are  of  much  help.  I  have  recently  had  under  my 
care  a  man  suffering  from  advanced  neurasthenia, 
whose  weight  had  dropped  from  eleven  stone  to 
between  eight  and  nine.     Under  the  administration  of 


16    THE  OEGANS  OF  INTERNAL  SECRETION 

a  mixed  extract  his  weight  is  now  (one  month  after 
the  commencement  of  treatment)  nearly  ten  and  a 
half  stone,  although  nothing  had  previously  been  able 
to  stop  the  loss  of  weight. 

In  the  Practitioner  for  January  and  February,  1915, 
will  be  found  many  able  articles  from  the  pens  of 
experts  on  the  subject  of  the  endocrine  glands.  These 
articles  discuss  fully  the  available  material  both  from 
the  standpoint  of  the  laboratory  and  the  bedside. 
A  perusal  of  these  numbers  will  well  repay  the  time 
occupied. 

To  obtain  the  best  results  from  the  therapeutic 
standpoint,  however,  a  knowledge  of  the  physiology 
of  the  Internal  Secretions  is  absolutely  essential.  The 
following  chapter  attempts  to  summarize  this  aspect 
of  the  subject. 


CHAPTER  I 

THE  PHYSIOLOGY  OF  THE  INTERNAL 
SECRETIONS 

Introduction. 

The  discovery  that  the  metabolism  of  the  body  can 
be  affected  by  the  administration  of  preparations  of 
organs  has  led  to  the  establishment  of  a  new  branch  of 
therapeutics — namely,  organo-therapy.  Not  that  this 
method  of  treatment  is  entirely  new;  indeed,  the  em- 
ployment of  animal  extracts  empirically  is  exceedingly 
old;  but  such  treatment  has  always  been  based  upon 
a  kind  of  homoeopathic  reasoning  and  not  upon  the 
physiological  knowledge  wThich  is  now  at  the  disposal 
of  the  clinician. 

The  point  of  importance  in  the  study  of  the  Internal 
Secretions  is  that  blood  flowing  through  an  organ  can 
acquire  characteristics  due  to  the  influence  exerted  by 
that  organ.  While,  therefore,  the  phrase  "  ductless 
glands  "  is  often  understood  to  mean  definite  bodies, 
such  as  the  thyroid,  suprarenal,  and  thymus,  the 
phrase  "  organs  of  internal  secretion  "  connotes  those 
structures  which  secrete  a  substance  influencing  or 
modifying  the  blood  in  its  passage  through  the  organ. 
The  importance  of  the  blood-stream  has  been  recog- 

17  2 


18    THE  OEGANS  OF  INTERNAL  SECRETION 

nized  since  the  time  of  Harvey;  and  that  it  could  be 
the  channel  through  which  diseases  could  be  conveyed 
was  naturally  the  next  step.  Further  researches  have 
only  emphasized  the  fact  that  it  is  to  the  composition 
of  the  blood,  and  to  the  changes  it  undergoes  under 
varying  conditions,  we  must  look  for  the  pathogenesis 
of  many  diseases.  The  nervous  system  as  a  means  of 
transmitting  messages  is  a  late  development  in  evolu- 
tion; the  humoral  channel  is  a  much  earlier  arrival. 
Primitive  life  responds  to  chemical  stimuli,  which  are 
slow  in  their  action,  and  these  have  been  superseded, 
so  far  as  speed  is  concerned,  by  the  nervous  system, 
much  as  the  horse  has  been  superseded  by  the  train  or 
the  automobile. 

In  1849  Berthold,  of  Gottingen,  experimented  by 
removing  the  testes  from  cocks  and  grafting  them  into 
another  part  of  the  body,  his  object  being  to  show 
that  they  secreted  a  substance  which,  when  absorbed 
by  the  blood,  produced  the  male  characters.  According 
to  Biedl,  to  this  physiologist  belongs  the  credit  of  first 
proving  the  existence  of  an  "  internal  secretion." 
Claude  Bernard  believed  that  the  glands  of  the  body 
secreted  both  an  external  secretion  and  an  internal 
secretion,  the  latter  being  delivered  straight  into  the 
blood.  Brown-Sequard  is  generally  admitted  to  be 
the  founder  of  the  practice  of  organo-therapy,  for  he 
was  the  first  to  demonstrate  the  value  of  administering 
extracts  of  glands. 

The  chemical  agents  which  excite  the  functions  of 
other  organs  have  been  termed  hormones;  in  fact,  this 


PHYSIOLOGY  OF  INTEENAL  SECRETIONS     19 

term  has  largely  been  adopted  to  denote  any  chemical 
— be  it  excitatory  or  depressant — which  is  secreted  into 
the  blood.  Schafer  has  suggested  that  the  term 
"  autacoid  "  should  be  used  generically  to  denote  an 
internal  secretion;  the  term  "  hormone,"  he  thinks, 
should  be  kept  for  an  internal  secretion  which  excites, 
to  distinguish  it  from  a  "  chalone,"  or  one  which  has 
an  inhibitory  action.  As,  however,  the  term  hormone 
is  in  more  or  less  general  use  to  denote  an  internal 
secretion,  we  shall  use  it  here  in  its  wide  meaning. 

Hormones. 

The  substances  which  exert  a  chemical  action  upon 
the  blood  in  its  passage  through  an  organ  have  been 
called  "  hormones  "  (6pfj,d(o  =  "  I  excite  ").  The  term 
owes  its  origin  to  Bayliss  and  Starling,  who  proposed 
its  use  for  those  physiological  substances  which  act  as 
chemical  stimulants.  Examples  of  this  are  to  be 
found  in  the  processes  of  digestion,  where  the  entrance 
of  the  chyme  into  the  small  intestine  causes  the  pro- 
duction of  secretin,  which  stimulates  the  liver,  pan- 
creas, and  intestinal  glands.  Again,  the  influence 
which  a  gland  like  the  thyroid  exerts  upon  other  glands 
and  their  secretions  is  apparent:  remove  the  gland  or 
its  secretion  and  the  entire  bodily  metabolism  is 
upset.  "  All  organs  which  supply  substances  which 
are  capable  of  exciting  or  in  any  way  of  affecting 
the  functions  of  other  organs  may  be  described  as 
1  hormone- producing  '  "  (Biedl).     "  Material  which   is 


20    THE  ORGANS  OF  INTERNAL  SECRETION 

passed  into  the  blood  or  lymph  from  any  tissue  or 
organ  of  the  body  forms  its  internal  secretion,  and 
organs  which  are  not  known  to  possess  any  other 
function  than  that  of  passing  such  material  into  the 
blood  or  lymph  are  internally  secreting  or  endocrine 
organs  "  (Schafer). 

It  is  well  known  that  not  only  glands  without  ducts 
(the  "  ductless  glands  "),  but  also  glands  with  ducts, 
"  epithelial  elements,"  mucous  membranes,  and  so  on, 
must  be  included  among  the  organs  of  internal  secre- 
tion if  they  supply  a  hormone  to  the  blood.  Little  is 
known,  however,  of  the  exact  form  in  which  the  hor- 
mones reach  the  blood-stream,  or  the  chemical  means 
by  which  they  modify  it.  Most  of  our  knowledge  has 
been  gained  by  experimental  physiology,  and  some  by 
clinical  medicine.  It  has  been  shown  that  removal  of 
the  thyroid  profoundly  affects  metabolism  and  always 
in  a  certain  definite  manner;  that  removal  of  the  para- 
thyroids (in  animals)  leads  to  symptoms  of  nervous 
excitability  and  death;  and  that  castration  is  followed 
by  changes  which  vary  within  certain  well-defined 
limits.  Therefore,  the  glands  in  question  contribute 
to  the  general  metabolism  some  substance,  the  loss  of 
which  is  followed  by  a  general  disturbance.  Now,  it 
is  obvious  that  this  substance  is  a  chemical  agent,  for 
experiments  by  grafting  have  proved  beyond  doubt 
that  the  missing  hormone  can  be  supplied  to  the  body 
if  the  gland  is  so  attached  that  its  contents  can  be 
delivered  into  the  blood. 

According  to  one  view,   only  those  organs  which 


PHYSIOLOGY  OF  INTEENAL  SECRETIONS     21 

possess  "  differentiated  epithelial  cells  "  can  justly  be 
regarded  as  "  internal  secretory  "  in  the  strict  sense  of 
the  term.  But  it  is  obvious  that  this  interpretation  of 
the  term  is  too  narrow,  for  the  chromaffin  tissue — the 
corner-stone  of  the  endocrine  system — would  be  ex- 
cluded. From  the  physiological  standpoint  all  organs, 
whether  possessing  a  duct  or  not,  which  exert  a  specific 
influence  on  the  blood  circulating  through  them  are  to 
be  regarded  as  organs  of  internal  secretion. 

As  we  noted  in  the  case  of  secretin,  where  one  chemical 
agent  stimulates  another,  which  in  turn  activates  a 
third,  we  have  a  process  started  depending  entirely 
upon  a  hormone- action.  The  internal  secretory  organs, 
then,  are  important  on  account  of  the  hormones 
which  they  secrete.  These  are  chemical  substances  of 
low  molecular  weight,  which  are  not  destroyed  by 
heating,  but  are  rendered  inert  by  prolonged  boiling. 
They  are  destroyed  by  oxidizing  agents,  and,  except 
in  the  case  of  thyro-iodin,  do  not  leave  the  body  in  the 
excretions. 

The  secretion  of  the  thyroid  gland,  or  thyro-iodin, 
consists  of  a  substance  rich  in  iodine  in  organic  com- 
bination, which  is  present  in  the  colloid  of  the  vesicles. 
Eemoval  of  the  thyroid  produces  symptoms  presently  to 
be  described.  The  secretion  of  the  adrenal  medulla,  first 
isolated  by  Takamine  as  ortho-dioxy phenyl- ethanol- 
methylamine,  is  present  in  the  proportion  of  1  part  to 
1,000  of  the  whole  gland.  Recent  work  on  the  subject 
of  the  chromaffin  system  has  caused  physiologists  to 
regard  this  tissue  as  even  more  important  than  formerly; 


22    THE  OEGANS  OF  INTERNAL  SECRETION 

and  some  authorities,  notably  Sajous,  attribute  to  the 
adrenal  system  influences  of  the  widest  nature.  Refer- 
ences to  his  views  on  this  subject  will  be  found  in 
Chapter  VI. 

Hormones  fall  roughly  into  two  classes,  according 
to  their  mode  of  origin.  They  may  be  formed  by 
definite  structures,  whose  sole  function  is  the  produc- 
tion of  the  product;  or  they  may  be  the  end  products 
of  metabolism.  The  secretion  of  the  thyroid  may  be 
regarded  as  an  example  of  the  former  class;  the 
formation  of  carbon  dioxide,  with  its  specific  action 
as  a  stimulant  upon  the  respiratory  centre,  is  a  hor- 
mone belonging  to  the  second  group.  The  regulation 
of  respiration  is  now  believed  to  be  due  to  chemical 
action.  It  is  not  regulated,  but  may  be  modified  by 
nervous  stimulation. 

Our  knowledge  of  the  exact  chemical  nature  of 
hormones  is  very  small.  It  is  known  that  there  is  a 
large  range  of  action  in  the  physiology  of  the  body, 
due  to  their  presence  in  the  blood-stream  and  in  some 
cases  their  specific  action  on  the  various  organs;  but 
their  exact  formation  and  action  is  not  always  known. 
Claude  Bernard's  original  theory  was  that  glandular 
products  modified  the  composition  of  the  blood;  while 
the  school  that  followed  Brown-Sequard's  ideas 
believe  that  the  internal  secretions  have  a  "  specific 
elective  power,"  which,  as  Gley  says,  is  "  properly  a 
physiological  idea."  "  What  there  is  characteristic 
about  this  ...  is  that  we  are  now  dealing  with  func- 
tional actions  which  have  neither  cause,  nor  r-eason,  nor 


PHYSIOLOGY  OF  INTERNAL  SECRETIONS     23 

an  end  of  their  own;  but  each  one  of  these  acts  depends 
on  another  physiological  action;  and  this  dependence 
appears  to  be  always  of  a  chemical  nature,  be  it  direct 
or  indirect,  being  accomplished  through  the  inter- 
mediary action  of  the  nervous  system."* 

From  this  standpoint  we  pass  naturally  to  a  con- 
sideration of  the  functional  correlation  of  the  various 
internal  secretions.  We  can  realize  that  the  theory 
of  inter-relationship  between  the  various  humoral  in- 
fluences of  the  body  goes  a  long  way  towards  influenc- 
ing many  physiological  and  some  pathological  facts 
which  have,  up  to  now,  puzzled  us.  They  can  be 
regarded  as  not  dissimilar  to  the  drugs  of  the  pharma- 
copoeia, for  they  are  present  in  the  body  to  be  utilized 
when  the  occasion  arises.  As  we  shall  see  in  dis- 
cussing the  relation  between  the  endocrine  organs  and 
the  nervous  system,  a  sudden  call  for  increased  energy 
is  responded  to  by  the  adrenals,  and  to  some  extent  by 
the  thyroid.  A  less  urgent  message  would  perhaps 
require  the  co-operation  of  other  hormones.  The 
growth  of  the  body  requires  the  action  and  inter- 
action of  many  internal  secretions,  the  thyroid,  pitui- 
tary, thymus,  suprarenals,  gonads,  and  digestive 
glands.  Indeed,  we  must  widen  our  view  where  such  a 
subject  as  growth  is  concerned,  and  believe  that  almost 
any  hormone,  if  missing,  may  disturb  the  development 
of  the  organs  with  their  attached  functions. 

As  we  have  already  said,  histological  facts  have  to 
be  considered  when  we  are  studying  hormone-produc- 
*  "  The  Internal  Secretions,"  by  E.  Gley,  p.  61. 


24    THE  ORGANS  OF  INTERNAL  SECEETION 

tion.     Epithelium  gives   us   a   locality;   its   secretion 
introduces  chemical  factors;  while  the  action  of  this 
secretion  invades  the  realm  of  physiology.     We  cannot 
afford  to  be  over-precise  in  discussing  which  hormones 
can  justly  be  included  among  the  internal  secretions, 
and  which  must  be  barred  because  they  fail  to  fulfil 
certain  criteria.     The  thyroid  gland,  for  example,  is, 
without  doubt,  an  organ  of  internal  secretion;  yet,  as 
Gley  points  out,  no  specific  chemical  has  yet  been 
found  in  the  venous  blood  of  that  organ.     Experiments 
in  animals  and  clinical  evidence  combine  together  to 
prove  that  this  gland  is  essential  to  health;  we  must, 
therefore,  accept  this  evidence  as  contributing  a  proof 
that  this,  and  probably  many  other,  hormones  pro- 
foundly influence  metabolism,  although  we  are  as  yet 
unable  to  point  to  the  exact  means  by  which  this  is 
brought   about.     The   inter-relationship   between   the 
various  hormones  and  the  manner  in  which  one  in- 
fluences another,  which  in  turn  activates  a  third,  has 
been  proved  since  the  work  of  Starling  on  secretin. 
The  combination  of  many  of  the  internal  secretions, 
and  the  manner  in  which  the  removal  of  one  upsets 
the  endocrine   balance,   can   best   be   understood    by 
studying  their  inter-relationships. 

The  Inter-Relations  of  the  Ductless  Glands. 

"While  the  theory  of  the  internal  secretions  dates 
back  for  years,  and  while  our  practical  knowledge  of 
their  importance  is  over  half  a  century  old,  it  is  only  of 


PHYSIOLOGY  OF  INTEENAL  SECRETIONS     25 

recent  years  that  we  have  realized  how  the  various 
hormones  act  and  inter-act  to  produce  normal  function. 
At  the  present  time  we  know  enough  of  the  ductless 
glands  and  their  inter-relation  to  convince  us  that 
normal  health  is  largely  dependent  upon  their  smooth 
workings. 

The  changes  in  metabolism  which  are  seen  in  myx- 
cedema  have  their  analogy  in  the  mental  sluggishness 
characteristic  of  this  state,  while  the  psychical  ex- 
citability of  hyperthyroidism  is  in  keeping  with  the 
speed  of  the  bodily  metabolic  changes.  Xo  part  of 
the  individual  appears  to  escape  when  once  a  vital 
chemical  becomes  exaggerated  or  eclipsed;  its  place  in 
the  physiological  dovetailing  must  be  exact  if  we  are 
to  expect  normal  health. 

The  thyro-parathyroid  apparatus  affords  us  an 
excellent  example  of  this,  as  experiments  upon  thyroid 
extirpation  show  very  clearly  the  effects  of  thyroid 
deprivation  upon  the  organism.  Early  experiments 
to  determine  the  exact  rule  of  the  thyroid  were  com- 
plicated by  one  factor — namely,  the  presence  of 
accessory  thyroids — thyroid  "  rests,"  and  those  small 
glands  the  parathyroids.  Again,  experimental  removal 
of  the  gland  showed  results  which  differed  according  to 
the  animal  operated  upon.  In  the  dog,  cat,  and 
monkey,  the  upper  parathyroid  is  usually  embedded 
in  the  substance  of  the  thyroid;  but,  as  Gley  has 
pointed  out,  in  the  rabbit  one  of  the  parathyroids  is 
constantly  detached  from  the  thyroid. 

This  factor  accounts  for  the  different  results  which 


26    THE  ORGANS  OF  INTERNAL  SECRETION 

were  recorded  after  thyroidectomy — in  some  cases 
tetany  following  thyroidectomy,  in  others  this  state 
not  supervening  upon  the  operation.  The  difference 
depended  upon  whether  all  parathyroid  tissue  was 
removed  with  the  thyroid,  or  whether  some  was  left 
behind.  In  the  former  case  the  animal  died,  usually 
within  a  few  days,  the  symptoms  consisting  of  nervous 
excitability,  exaggeration  of  the  reflexes,  clonic  con- 
tractions of  the  limbs,  and  undue  irritability  to  any 
stimuli,  convulsions  and  sometimes  diarrhoea,  and 
vomiting. 

This  state  is  known  as  "  tetany,"  and  is  undoubtedly 
due  to  loss  of  the  parathyroids,  the  result  being  brought 
about  by  action  on  the  lower  neurons,  for  Horsley 
stated  that  it  was  not  affected  by  ablation  of  the 
cerebral  cortex.  Even  more  striking  in  the  etiology  of 
this  state  is  the  fact  that  it  is  relieved  by  injections  of 
parathyroid  extract,  or  by  the  grafting  of  parathyroid 
gland  into  the  animal.  In  one  animal,  operated  on 
by  Vassale,  in  whom  three  of  the  parathyroids  had 
been  removed,  the  animal  was  liable  to  convulsions 
during  pregnancy,  and  when  flesh  food  was  given  the 
convulsions  were  worse.* 

The  effects  of  removal  or  atrophy  of  the  thyroid 
gland  are,  briefly,  as  follows:  adiposity,  thickening  of 
the  integument,  loss  of  hair,  loss  of  muscular  tone, 

*  In  some  cases  of  exophthalmic  goitre,  possibly  of  toxic  origin, 
many  of  the  symptoms  are  relieved,  certainly  in  some  cases 
which  the  writer  has  had  under  observation,  by  the  withdrawal 
of  animal  food. 


PHYSIOLOGY  OF  INTERNAL  SECRETIONS     27 

anaemia,  lowering  of  the  bodily  temperature,  with 
sensations  of  chilliness,  and  retardation  of  the  rate  of 
the  heart.  There  is  an  increased  tolerance  to  carbo- 
hydrates, so  that  large  quantities  of  sugar  and  starch 
have  to  be  given  before  glycosuria  is  produced,  while 
the  mental  functions  become  sluggish  and  the  intellect 
clouded.  As  is  well  known,  juvenile  myxoedema  or 
cretinism — a  condition  presenting  most  of  the  above 
features — is  due  to  an  absence  or  degeneration  of  the 
gland  before  puberty,  but  associated,  of  course,  with 
diminished  growth. 

Turning  to  the  role  of  the  thyroid  in  health,  we  may 
summarize  its  functions  by  saying  that  it  is  one  of  the 
most  important  "  regulators  of  metabolism "  which 
the  body  possesses.  Its  action  upon  the  circulation 
is  that  of  a  stimulant;  its  secretion  is  an  essential 
chemical  for  the  nutrition  of  the  integument  and  the 
epidermal  structures  as  a  whole.  When  thyroid  de- 
ficiency is  present  there  is  loss  of  elasticity  of  the  skin, 
caries  of  the  teeth,  loss  of  lustre  in  the  hair,  ridged  and 
dull  nails,  and  frequently  pruritus.  The  rule  of  the 
thyroid  secretion  is,  then,  to  regulate  the  elimination 
of  the  body,  to  increase  the  tone  of  the  muscles,  to 
assist  in  the  nutrition  of  all  the  cells,  particularly  those 
of  the  epidermal  appendages,  and  to  prevent  accumu- 
lation of  waste-products,  especially  in  the  subcutaneous 
tissues  and  muscles.  Hence  in  thyroid  deprivation  we 
find  that: 

1.  The  protein  metabolism  is  decreased. 

2.  The  fat  metabolism  is  probably  likewise  lessened. 


28  THE  ORGANS  OF  INTERNAL  SECRETION 

3.  The  carbohydrate  metabolism  is  markedly  re- 
tarded. 

We  are  justified  in  assuming  that  where  symptoms 
of  retarded  metabolism  and  sluggish  circulation  are 
present,  we  shall  find  that  thyroid  under- action  is 
present.  Furthermore,  the  chromaffin  system,  which 
is  concerned  in  the  mobilization  of  sugar,  is  affected 
adversely  by  the  removal  of  the  secretion  of  the 
thyroid;  probably  this  may  be  another  factor  in  the 
production  of  increased  sugar  tolerance  in  thyreopriva. 

The  results  of  administering  extract  of  the  thyroid 
are  very  striking,  and  will  be  considered  in  detail  in 
subsequent  chapters.  Here  we  are  concerned  more 
with  the  physiology  of  the  gland  and  its  inter-relation- 
ship with  other  of  the  endocrine  organs,  and  with  the 
nervous  system.  Dealing  with  the  first  group,  and 
taking  the  adrenal  glands,  is  there  a  relation  between 
these  glands  and  the  thyroid  ?  Eppinger,  Falta,  and 
Rudinger  have  shown  that  adrenalin,  which  normally, 
when  injected,  causes  glycosuria,  no  longer  does  so 
when  the  thyroid  has  been  removed,  but  does  so  after 
extract  of  thyroid  has  been  administered.  But  opinion 
is  not  unanimous  in  supporting  the  result  which* 
appears  to  indicate  this  inter-relationship.  Gley  sums 
up  the  question  as  follows:  "  (a)  Is  the  thyroid  secretion 
really  an  excitant  of  the  suprarenal  ?  and  does  the 
suprarenal  blood  therefore  contain  more  adrenalin 
after  the  injection  of  thyroid  extract  ?  (b)  Do 
extracts  of  suprarenal  glands  of  thyroidectomized 
animals  which  succumbed  to  the  operation  contain  less 


PHYSIOLOGY  OF  INTEENAL  SECRETIONS     29 

adrenalin  ?  On  these  two  points  I  have  collected  a 
large  number  of  facts.  These  facts  prove  that  the 
adrenals  of  thyroidectomized  animals  do  not  contain 
less  active  adrenalin  than  those  of  normal  animals  and, 
furthermore,  that  the  suprarenal  blood  does  not  become 
richer  in  adrenalin  after  the  injection  of  thyroid  extract 
in  physiological  doses  than  after  that  of  any  other 
organic  extract,  at  least  of  those  which  have  been 
tested  in  the  experiments  of  Gley  and  Quinquaud — 
viz.,  hepatic,  pancreatic,  testicular,  and  renal."* 

It  will  be  seen  from  this  quotation  that  the  reciprocal 
action  of  the  thyroid  and  adrenals  is  not  supported  by 
Gley's  work;  rather  would  it  seem  that  the  results 
referred  to  which  appear  to  point  to  this  action  might 
conceivably  be  due  to  the  injection  of  any  organic 
extract  and  not  to  the  fact  that  it  was  thyroid  extract 
which  was  utilized. 

A  reciprocal  action  between  the  thyroid  and  the 
pancreas  has  been  suggested,  and  Lorand  says  that 
"  extirpation  of  the  thyroid  suppresses  glycosuria  in 
depancreatinized  animals. "f  Gley  doubts  whether 
this  is  so,  and  suggests  that  this  explanation  ignores 
many  important  points.  Again,  inter-relationship 
between  the  thyroid  and  the  sexual  organs  appears  to 
exist;  certainly  many  suggestive  signs  point  to  this 
conclusion.  The  testis  and  the  thyroid  appear  to 
have  a  relation,  likewise  the  ovary ;  and  it  is  well  known 

*  "  The   Internal   Secretions,"   by  G.    Gley   (translated  by 
Fischberg),  pp.  206-207. 
t  Ibid.,  p.  208. 


30    THE  ORGANS  OF  INTERNAL  SECRETION 

that  the  thyroid  gland  tends  to  enlarge  at  the  times 
of  puberty,  the  catamenia,  and  the  menopause.  The 
ovaries  exert  an  inhibitory  action  upon  the  thyroid, 
the  size  of  the  latter  gland  increasing  after  castration. 

In  some  cases  of  cretinism,  the  anterior  lobe  of  the 
pituitary  has  been  found  to  be  enlarged,  but  this  is 
not  always  so.  It  has  been  suggested  that  this  en- 
largement is  due  to  a  compensatory  hypertrophy — a 
kind  of  "  defensive  balancing "  of  the  endocrine 
system.  The  inter-relation  between  the  thyroid  and 
the  pituitary  appears  to  be  a  close  one;  for  experimental 
removal  of  the  former  causes  hypertrophy  of  the 
latter,  and  Cushing  states  that  removal  of  the  pituitary 
in  young  dogs  causes  hypertrophy  of  the  thyroid. 

The  interaction  of  the  thyroid  and  the  thymus  is 
less  well  established,  although  some  results  suggestive 
of  such  a  relationship  have  been  recorded.  The 
thymus  is  usually  hypertrophic  in  Graves'  disease,  and 
it  is  therefore  believed  to  exert  an  antagonizing  action. 
The  thyroid  and  parathyroids  are  believed  to  exist  in 
antagonistic  relationship,  certainly  in  so  far  as  their 
action  upon  the  nervous  system  is  concerned.  The 
parathyroids  resemble  the  thymus  in  this  respect,  for 
their  removal  is  followed  by  nervous  symptoms. 
Paton  suggests  that  both  exert  "  a  depressing  or 
regulating  effect  upon  the  spinal  synapses,  an  action 
opposite  to  that  of  the  thyroid." 

There  is  a  definite  antagonism  between  the  pan- 
creatic secretion  and  the  chromaffin,  certainly  in  so 
far  as  the  mobilization  of  sugar  is  concerned.     The 


PHYSIOLOGY  OF  INTERNAL  SECRETIONS      31 

internal  secretion  of  the  pancreas  checks  the  mobilizing 
of  sugar,  while  adrenalin  hastens  it.  It  is  believed  that 
adrenalin  acts  by  stimulating  the  sympathetic  endings 
fn  the  liver;  perhaps,  as  Paton  suggests,  "  the  endo- 
crinous secretion  of  the  pancreas  inhibits  them." 
The  interaction  of  the  pancreas  and  the  thyroid  is 
indicated  by  the  occurrence  of  glycosuria  in  Graves' 
disease  and  by  the  experiment  of  Lorand,  which 
showed  that  removal  of  the  thyroid  in  a  dog  suffering 
from  pancreatic  diabetes  reduced  the  glycosuria;  also 
by  the  observation  of  Eppinger,  Falta,  and  Eudinger, 
already  referred  to,  that  after  thyroidectomy  adrenalin 
produces  glycosuria  less  readily. 

There  is  a  reciprocal  action  between  the  gonads  and 
the  thyroid,  for  thyroidectomy  stops  the  growth  of  the 
sexual  glands,  although  castration  does  not  have  a 
similar  effect  upon  the  thyroid.  Both  the  thyroid 
and  the  gonads,  moreover,  have  a  stimulating,  al- 
though not  an  exactly  similar,  effect  upon  growth. 
The  testes  are  helped  in  this  relation  by  the  thymus, 
for  this  gland  appears  to  check  the  growth  of  the 
testes,  while  the  latter  exert  a  similar  action  on  the 
thymus. 

The  relation  between  the  gonads  and  the  pituitary 
is  interesting.  Destroying  the  pituitary  causes  atrophy 
of  the  gonads,  but  castration  causes  hypertrophy  of  the 
former  gland;  the  pituitary  therefore  has  a  stimulating 
action  on  the  gonads,  but  these  have  an  inhibitory 
action  on  the  pituitary  (Paton).  Both  exert  a 
stimulating  action  on  growth,  while  the  pituitary,  when 


32    THE  ORGANS  OF  INTERNAL  SECRETION 

unchecked  by  the  controlling  action  of  the  gonads, 
produces  gigantism  and  acromegaly. 

There  is  a  suggested  relationship  between  the  sex 
organs  and  the  parathyroids,  which  is  seen  in  the 
observation  that  pregnancy  increases  the  symptoms  of 
hypo-parathyroidism.  Little  is  known,  however,  of 
this  inter-relation. 

Interesting  observations  as  to  the  relationship 
between  the  adrenals  and  the  sexual  organs  have  been 
made.  It  is  believed  that  this  relation  is'a  particularly 
close  one;  indeed,  Sajous  suggests  that  the  testicle 
does  not  produce  an  internal  secretion,  but  that  the 
adrenal  rests  which  are  contained  in  this  organ  are 
responsible  for  the  "  elaboration  of  the  sperm." 
Several  instances  are  on  record  in  which  precocious 
development  and  early  appearance  of  the  secondary 
sexual  characteristics  have  been  associated  with  a 
tumour  of  the  adrenal  body;  moreover,  on  the  removal 
of  the  tumour  these  signs  have  subsided.*  Further, 
the  symptoms  and  signs  of  testicular  tumour  (from 
the  cells  of  Leydig)  are  precisely  those  seen  in  a 
growth  of  the  adrenal  cortex.  Tumours  in  the  latter 
situation  occur  usually  in  children  and  are  associated 
with  premature  development,  so  that  a  child  of  seven 
or  ten  years  may  have  the  characteristics  of  an  adult 
woman;  marked  growth  of  hair  on  the  head  and  body, 
and  a  tendency  to  male  characteristics,  such  as  a  deep 
voice,  and  over- development  of  the  clitoris.     Sajous 

*  Quoted  by  Sajous,  "  Internal  Secretions  and  Principles  of 
Medicines,"  pp.  474-476 


PHYSIOLOGY  OF  INTERNAL  SECEETIONS      33 

concludes,  therefore,  that  "  it  is  to  the  secretion  of  the 
adrenal  tissues,  wherever  situated,  that  the  male 
characteristics  are  due."* 

It  is  interesting  to  compare  the  above  description  of 
the  signs  of  adrenal  over- activity  with  those  typical 
of  hypo-adrenia — namely,  muscular  weakness,  loss  of 
flesh,  feeble  cardiac  action,  low  blood-pressure,  con- 
stipation, deficient  growth  of  hair,  pallor,  and  mental 
sluggishness.  These  symptoms,  of  course,  when  due 
to  disease  of  the  suprarenal  bodies,  constitute  the 
disorder  known  as  Addison's  disease. 

The  ovary  possesses  analogous  properties — from  the 
point  of  view  of  the  internal  secretions — to  the  testis, 
up  to  a  certain  point,  but  then  the  analogy  ceases. 
Removal  of  the  ovaries  in  the  young  female  produces 
results  similar  to  those  seen  after  castration  in  the 
young  male — namely,  an  infantile  type  of  the  genital 
organs  and  a  non- development  of  the  mamma?;  while 
after  ovariectomy  in  the  adult  there  is  a  retrogressive 
change  seen  in  the  uterus  and  mammae,  and  a  cessation 
of  menstruation.  Again,  the  influence  on  metabolism 
of  the  ovarian  secretion  is  analogous  to  that  of  the 
testis — in  other  words,  it  increases  oxidation  and 
metabolism,  so  that  its  removal  produces  obesity  and 
a  sluggish  circulation. 

It  is  claimed  by  many  authorities  that  administration 
of  ovarian  extract  increases  oxidation,  particularly  of 
phosphorus  products,  hydrocarbons,  and  fats.  The 
clinical  reports  of  the  results  following  ovarian  organo- 

*  Ibid.,  p.  477. 


34    THE  ORGANS  OF  INTERNAL  SECRETION 

therapy  are  striking,  and  there  can  be  little  doubt  that 
this  substance  possesses  a  real  value  in  enhancing  the 
deficient  metabolism  consequent  upon  ovarian  atrophy. 

The  question  "  To  what  part  of  the  ovary  is  this 
action  due  ?"  is  not  so  easy  to  answer.  The  three 
possibilities  are  the  interstitial  cells,  the  Graafian 
follicles,  and  the  corpora  lutea.  The  latter  possess,  it 
is  said,  all  the  properties  which  characterize  the 
chromaffin  tissue,  and,  furthermore,  show  the  signs 
suggestive  of  an  internal  secretory  organ,  being 
extremely  vascular,  and  related  in  development 
intimately  with  the  mammary  gland,  destruction  of 
the  corpus  luteum  arresting  the  development  of  the 
mammae. 

The  interstitial  gland,  on  the  other  hand,  behaves 
in  many  ways,  as  do  the  corpora  lutea.  It  attains  to 
greatest  development  during  pregnancy  and  becomes 
enlarged  during  menstruation.  This  body  is  believed 
to  possess  many  of  the  characteristics  of  adrenal  tissue. 
"  We  know  that,  in  addition  to  the  Graafian  follicles, 
the  ovary  contains  two  other  tissues,  both  of  which, 
from  the  nature  of  their  structure,  might  possess  an 
internal  secretory  function,  but  which  in  their  origin 
differ  fundamentally  from  one  another.  These  are 
the  corpus  luteum,  which  is  derived  from  the  epithe- 
lium, and  the  interstitial  stroma  cells,  which  have  a 
connective-tissue  origin.  That  the  interstitial  stroma 
cells  possess  a  secretory  function  is  suggested  by  the 
presence  of  fat  granules  and  other  secretory  enclosures, 
as  well  as  a  certain  resemblance,  commented  upon  by 


PHYSIOLOGY  OF  INTERNAL  SECRETIONS     35 

many  (Mulon,  Wallart),  to  the  cells  of  the  suprarenal 
cortex."* 

After  discussing  the  theories  which  connect  ovula- 
tion and  menstruation,  Biedl  says:  "Hence  we  are 
forced  to  assume  a  continuous  production  of  the 
hormone  by  which  these  changes  are  effected,  the 
source  of  which  can  only  be  either  in  the  Graafian 
follicle  itself  or  in  the  interstitial  tissue.  But  the 
Graafian  follicles  are  already  present  in  the  immature 
ovary,  and  for  that  reason  they  can  hardly  be  credited 
with  the  same  significance  in  this  connection  as  the 
interstitial  gland,  which  attains  its  full  development 
at  puberty,  shows  signs  of  a  cyclic  increase  of  function 
corresponding  with  menstruation,  and  which,  at  the 
climacteric,  undergoes  involution,  "y 

Sajous  believes  that  the  secondary  sex  characteris- 
tics in  the  female  owe  their  origin  to  the  interstitial 
cells,  which  "  correspond  morphologically  and  chemi- 
cally with  those  of  the  adrenal  cortex."  The  analogy 
is  clear,  but  he  states  definitely  that  these  cells  are  not 
the  same  structure  as  the  cells  of  Ley  dig  in  the  male: 
and  he  adds  that  "  there  is  no  true  internal  secretion 
of  the  ovaries,  the  products  of  the  Graafian  follicles 
and  their  corpora  lutea  and  of  the  interstitial  stroma 
cells  being  derived  mainly  from  adrenal  rests  in  those 
cells." 

We  have  discussed  the  inter-relationship  of  the 
ductless  glands,  and  shown  that  removal  of  one  secre- 

*  "  The  Internal  Secretory  Organs,"  p.  401. 
t  Ibid,,  p.  403. 


36    THE  ORGANS  OF  INTERNAL  SECRETION 

tion  produces  effects  which,  in  many  instances,  arise 
as  the  result  of  the  absence  of  the  secretion  and  its 
"  balancing  power."  We  must  now  consider  the 
question,  "  How  is  this  relationship  governed  ?" 

It  is  at  once  obvious  that  the  controlling  factor  may- 
be chemical  or  it  may  be  nervous.  In  other  words, 
the  internal  secretions  may  produce  their  own  control 
by  chemical  balancing,  or  the  helm  may  be  controlled 
from  the  central  nervous  system.  The  effect  of  a  graft 
upon  the  body  is  strongly  suggestive  that  the  chemical 
action  is  the  prominent  factor;  for  it  matters  not  in 
what  part  of  the  body  the  graft  is  implanted,  so  long 
as  the  secretion  arising  in  the  gland  finds  its  way  into 
the  blood-stream,  the  effects  of  the  extirpation  of  the 
gland  are  abolished  or  delayed.  This  would  scarcely 
be  so  if  nervous  stimuli  were  essential  to  the  produc- 
tion of  a  particular  hormone.  On  the  other  hand,  it 
would  be  foolish  to  assume  that  the  inter-relationships 
were  purely  chemical  and  entirely  free  from  the  super- 
vision of  the  nervous  system. 

Turning  for  a  moment  to  the  digestive  system,  we 
know  that  the  stimulus  which  excites  salivary  secretion 
is  often  nervous,  and  that  gastric  secretion  depends, 
at  all  events  for  its  commencement,  upon  the  same 
stimulant.  Subsequent  digestion,  it  is  true,  is  carried 
on  largely  by  chemical  messages.  Again,  the  produc- 
tion of  adrenalin  is  under  the  control  of  the  nervous 
system,  although  its  function  is  assisted,  correlated, 
and  sometimes  neutralized,  by  chemical  agents. 

The  answer  to  our  question  is,  on  the  face  of  it, 


PHYSIOLOGY  OF  INTEKNAL  SECRETIONS     37 

exceedingly  difficult,  and,  moreover,  is  complicated  by 
the  fact  that  removal  of  an  organ  is  not  invariably 
followed  by  the  same  result.     We  have  already  seen 
that  in  some   cases   of  hypothyroidism  the   anterior 
lobe  of  the  pituitary  is  enlarged,  but  this  is  not  always 
so.     It  is  possible,  as  Paton  suggests,  that  the  enlarge- 
ment, when  present,  is  a  defensive  one,  and  that  its 
absence  makes  the  condition  of  the  individual  worse. 
The  part  played  by  the  nervous  system  in  the  control 
of  the  endocrinous  glands  can,  however,  scarcely  be 
overlooked,  or  even  despised,  in  view  of  the  results  of 
recent  research.     We  know  that  intense  pain  produces 
an  increased  flow  of  adrenalin,  and  that  its  pathway 
is  via  the  sympathetic  system.     Emotional  activity,  if 
sufficiently  intense,   is   followed    by  a   similar  result. 
The  similarity  between  the  chromaffin  system  and  the 
sympathetic  is  exceedingly  close,  and  the  former  is  the 
keystone  of  the  endocrine  system.* 

It  would  seem,  therefore,  that  there  is  an  interaction 
of  a  chemical  nature,  which  functions  as  a  control; 
and  the  evidence  serves  to  show  that  control  is  exer- 
cised, certainly  in  some  instances,  by  the  nervous 
system.  With  the  facts  at  our  disposal  we  cannot 
answer  the  question  more  certainly,  but  must  await 
the  establishing  of  fresh  evidence. 

*  This  subject  is  discussed  at  greater  length  in  Chapter  XI. 


CHAPTER  II 

THE  THYROID  AND  PARATHYROID  GLANDS 

In  the  Introduction  we  briefly  reviewed  the  present 
place  of  the  endocrine  glands  in  medicine,  and  sug- 
gested some  practical  points  in  connection  with 
hormone- therapy.  We  now  propose  to  discuss  in  a 
little  more  detail  the  more  important  of  the  ductless 
glands,  laying  emphasis  upon  the  known  results  of 
administration  of  the  extract  of  these  glands,  and  the 
signs  pointing  to  deficiency  or  excess  of  secretion. 

Naturally,  the  thyroid  gland  first  deserves  our 
attention,  and  for  several  reasons.  More  is  known 
of  its  characteristics,  secretion,  functions,  and  dis- 
orders; it  takes  a  particularly  important  place  in 
medicine  on  account  of  the  frequency  with  which 
disorders  of  its  functions  are  encountered ;  and,  finally, 
of  all  the  ductless  glands  whose  secretions  have  been 
utilized  in  the  form  of  extracts  for  oral  or  hypodermic 
injections,  the  thyroid  gland  has  given  the  best  and 
most  astonishing  results.  From  the  moment  when 
G.  E.  Murray  first  published  the  results  achieved  by 
administering  thyroid  extract  to  a  patient  suffering 
from  myxcedema  (October  10,  1891),  great  interest 
has  been  aroused  in  the  practice  of   organo- therapy, 

38 


THYROID  AND  PARATHYROID  GLANDS     39 

an  interest  which  Brown-Sequard's  previous  state- 
ments on  the  results  of  feeding  with  testicular  extract 
had  failed  to  arouse. 

In  1890,  Vassale  in  Italy  and  Gley  in  France  experi- 
mented with  injections  of  thyroid  extract  to  animals 
who  had  been  deprived  of  their  thyroids,  and  demon- 
strated that  these  animals  could  be  kept  alive  by 
such  injections.  This  was  followed  shortly  afterwards 
by  the  application  of  this  discovery  to  therapeutics, 
when  Murray  treated  his  case  of  myxoedema  by 
thyroid  extracts  and  established  that  this  condition 
could  be  cured  by  these  means.  Previous  to  this 
date,  Gull  and  Ord  in  England  had  investigated 
myxoedema,  and  Kocher  had  described  a  condition 
following  the  removal  of  the  thyroid,  which,  from  the 
similarity  of  its  symptom-complex,  was  shown  to  be 
identical  with  the  spontaneous  condition  already 
named  myxoedema. 

As  far  back  as  1859,  Schiff  discovered  the  fatal 
result  which  accrued  from  the  total  removal  of  this 
gland,  and  later,  when  Kocher  described  "  cachexia 
strumipriva,"  or  the  condition  of  post-operative 
myxoedema  which  followed  so  many  of  his  early 
operations  for  goitre,  this  fact  attracted  wide  attention. 
Schiff  and  subsequent  observers  also  discovered  that 
transplanting  the  gland  beneath  the  skin  relieved  the 
symptoms.  Unfortunately,  it  has  now  been  shown 
that  an  implanted  gland  is  very  liable  to  absorption, 
and  thus  to  lose  its  utility. 

These    researches    had    established    the    fact    that 


40    THE  ORGANS  OF  INTERNAL  SECRETION 

removal  of  the  thyroid  gland  was  followed  by  a  train 
of  symptoms  which  constituted  the  condition  named 
"  myxcedema."*  A  fresh  factor  then  arose,  on  ac- 
count of  the  discovery  of  two  pairs  of  small  glands, 
situated  on  either  side  of,  and  deep  to,  the  lateral 
lobes  of  the  thyroid,  which  received  the  name  of 
"  parathyroids."  It  was  maintained  by  some  authori- 
ties that  the  symptoms  which  followed  the  removal 
of  the  thyroid  gland  were  due  to  the  removal  of  these 
small  glands,  and  in  support  of  this  theory  it  was 
adduced  that,  while  removal  of  the  thyroid  alone  was 
not  usually  fatal,  removal  of  both  thyroid  and  para- 
thyroids proved  rapidly  fatal.  On  the  other  hand, 
some  observers  maintained  that  it  was  impossible 
to  remove  the  parathyroids  without  alto  interfering 
with  the  integrity  of  the  thyroid.  Forsyth  concludes, 
from  the  result  of  his  investigations,  that  the  para- 
thyroids have  no  connection  with  tetany,  and  in  this 
he  is  in  opposition  to  most  observers.  We  shall  have 
more  to  say  about  this  when  we  are  dealing  with  the 
functions  of  the  parathyroids. 

Histology  and  Physiology  oS  the  Thyroid  Gland. 

The  thyroid  gland  is  developed  by  a  median  out- 
growth from  the  entoderm  lining  the  pharynx  between 
the  first  and  second  branchial  pouches.  A  solid  mass 
of  cells  bifurcates  at  the  upper  end  of  the  trachea:  the 

*  This  name  came  into  existence  on  account  of  the  believed 
existence  of  excess  of  mucin  in  the  subcutaneous  tissues  in  these 
cases. 


THYEOID  AND  PARATHYROID  GLANDS    41 

median  portion  becomes  the  thyro- glossal  duct,  which 
afterwards  becomes  obliterated;  the  lateral  portions 
divide  into  many  branches  and  form  hollow  tubes, 
which  become  closed  vesicles.  The  thyro-glossal 
duct,  through  which  the  secretion  was  originally  dis- 
charged, becomes  obliterated,  the  foramen  caecum  at 
the  base  of  the  tongue  remaining  to  mark  the  site. 
Langdon  Brown  suggests  that  thyroid  extract  is 
absorbed  unaltered  from  the  alimentary  tract  because 
the  duct  originally  carries  the  thyroid  secretion 
there. 

The  thyroid  gland,  therefore,  belongs  to  the  group  of 
ductless  glands — that  is  to  say,  its  secretion  is  poured 
into  the  blood-stream  direct,  and  not  by  means  of  a  duct. 
It  is  situated  in  the  neck,  and  consists  of  two  lobes, 
one  on  each  side  of  the  trachea,  extending  upwards 
to  the  thyroid  cartilage,  covering  its  inferior  cornu 
and  part  of  its  body.  Joining  these  two  lobes  is  the 
isthmus.  The  gland  is  surrounded  by  a  capsule,  and 
is  composed  of  vesicles  lined  with  cylindrical  or  cubical 
cells.  These  vesicles  contain  the  typical  colloid 
material,  iodothyrin,  which  is  composed  of  iodine 
in  combination  with  an  active  principle  which  has 
the  characters  of  a  globulin.  Its  recognition  we  owe 
to  Buamann  of  Freiburg,  who  discovered  its  existence 
in  1896.  Herbivora  possess  it  in  abundance,  as  most 
vegetables  contain  iodine.  The  weight  of  the  gland 
varies  between  32  and  60  grammes;  it  is  larger  in 
females  than  in  males,  and  undergoes  changes  in  size 
at  the  menstrual  periods,  and  at  such  times  as  puberty 


42     THE  ORGANS  OF  INTERNAL  SECRETION 

and  the  climacteric;  it  is  liable  to  swell  under  marked 
excitement  and  during  emotional  strain. 

The  colloid  with  which  the  vesicles  are  filled  plays 
an  important  part  in  general  bodily  metabolism.  In 
man  there  is  nearly  always  sufficient  for  it  to  be  dis- 
covered analytically  (in  normal  health),  but  Wells 
states  that  the  actual  amount  varies  with  the  locality. 
It  is  scanty  in  young  children  and  in  parenchymatous 
goitre;  unusually  high  in  exophthalmic  goitre.  It  has 
been  suggested  that  an  important  function  of  the 
thyroid  gland  is  to  control  the  iodine  metabolism  of 
the  body. 

Now  what  are  the  results  of  removal  of  the  gland 
in  man  ?  When  we  come  to  review  the  knowledge 
which  experimental  physiology  has  given  us,  we  are 
at  first  rather  bewildered  by  the  apparent  contradiction 
which  faces  us.  Early  observations  upon  the  effects 
which  followed  the  removal  of  the  gland  in  animals 
showed  that  in  carnivora  the  effects  were  very  severe, 
and  often  fatal,  tetany  supervening  and  the  animal 
dying  from  cachexia.  In  herbivora,  however,  the 
results  of  such  an  operation  were  often  exceedingly 
slight,  and  were  confined  to  a  slight  cachexia,  but 
sometimes  a  rapidly  fatal  result  ensued.  The  first 
inference  to  be  drawn  from  this  was  that  a  meat  diet 
was  the  important  factor  which  accounted  for  the 
difference  between  the  effects  in  carnivorous  and  her- 
bivorous animals.  Gley,  however,  showed  that  the 
explanation  was  quite  different,  and  he  proved  that 
the   parathyroids   (one   pair,   now   usually   known   as 


THYROID  AND  PARATHYROID  GLANDS    43 

the  "  external  parathyroids ")  were  responsible  for 
the  wide  difference  in  the  results.  He  demonstrated 
that  these  small  glands  were  so  situated  in  carnivora 
that,  when  the  thyroid  was  removed,  the  parathyroids 
were  also  removed;  whereas  in  herbivora  they  were 
as  habitually  left  behind.  When  the  operations  were 
made  identical  the  results  were  approximated. 

This  originated  the  view  now  widely  held,  which 
regards  the  nervous  symptoms  following  removal  as 
attributable  to  the  loss  of  the  parathyroids — the 
effects  of  thyroid  removal  alone  being,  in  the  young 
a  condition  analogous  to  cretinism,  in  the  adult  a 
cachectic  condition.  Indeed,  in  the  young  animal  the 
effects  of  thyroid  extirpation  are  much  more  marked 
than  in  the  adult  animal.  A  few  of  the  changes 
produced  are  striking.  As  we  have  already  said,  a 
cretinoid  condition  results,  with  delayed  ossification 
of  epiphyses,  diminished  development  of  the  bones 
of  the  skull,  protuberant  abdomen,  relaxation  of  the 
ligaments  of  the  spinal  column,  and  sexual  infantilism. 
Alterations  in  the  growth  of  the  hair  are  observed  in 
some  species,  and,  most  interesting  of  all,  an  extensive 
atheromatous  degeneration  of  the  aorta  is  found, 
which  bears  out  the  hypothesis  that  the  function  of 
this  gland  is  concerned  with  calcium  metabolism. 
Previous  to  this  discovery  Horsley  had  surmised  that 
many  of  the  features  of  thyroid  inadequacy  resembled 
those  which  characterize  senile  decay. 

Where  thyroid  secretion  is  excessive,  we  know  that 
there  is  increased  calcium  leaving  the  body;  and,  in 


44     THE  ORGANS  OF  INTERNAL  SECRETION 

those  patients  exhibiting  deficiency  of  thyroid,  we  may 
assume  that  increase  of  the  calcium  salts  at  the  disposal 
of  the  metabolism  results  in  an  atheroma — a  laying 
down  of  this  substance  in  the  walls  of  the  arteries. 

After  thyroid  extirpation  there  are  several  changes 
which  deserve  special  mention.  There  is  a  marked 
retardation  in  metabolism  in  general,  nitrogenous 
metabolism  is  greatly  reduced,  fat  metabolism  is 
likewise  diminished,  as  the  tendency  to  the  deposition 
of  fat  in  myxoedema  shows.  The  animal  without  a 
thyroid  exhibits  excessive  tolerance  to  carbohydrates; 
it  can  take  abnormally  large  amounts  without  suffer- 
ing from  glycosuria.  The  reduction  in  the  metabolic 
exchanges  naturally  diminishes  heat  production,  and 
this  point  is  of  interest  from  the  practical  standpoint, 
human  beings  with  deficient  thyroid  secretion  being 
more  susceptible  to  cold,  and  suffering  increased 
discomfort  in  the  winter  months.  As  opposed  to 
this,  patients  with  Graves'  disease  rarely  suffer  any 
inconvenience  from  cold,  but  feel  the  heat  of  the 
summer  months  to  be  almost  insupportable.  As  is 
well  known,  they  are  nervous  and  restless,  and  the 
increased  tissue  wastage  produces  a  rapid  loss  of  flesh, 
and  in  some  cases  actual  emaciation. 

The  Parathyroid  Glands. 

Turning  now  to  the  parathyroids,  whose  existence, 
it  will  be  remembered,  is  of  more  recent  discovery,  we 
find  that  there  are  two  pairs  of  these  glands,  situated, 
as  we  have  already  said,  in  close  proximity  to  the 


THYEOID  AND  PAKATHYEOID  GLANDS    45 

lateral  lobes  of  the  thyroid  gland  itself.  In  structure 
they  bear  some  resemblance  to  this  latter  gland, 
resembling  it,  however,  more  in  its  embryonic  charac- 
teristics. They  are  formed  of  columns  of  granular 
epithelium  cells,  and  show  a  very  vascular  connective 
tissue  between  these.  It  has  been  stated  that,  if 
these  glands  are  left  when  the  thyroid  has  been  re- 
moved, they  undergo  a  marked  hypertrophy. 

To  Sandstrom  belongs  the  credit  of  first  accurately 
describing  these  little  glands.  His  view  was  that  they 
were  in  reality  embryonic  rests  of  thyroid  tissue 
proper.  At  the  present  time,  although  our  knowledge 
of  their  functions  has  advanced  somewhat,  much  of 
the  knowledge  we  possess  may  be  described  as  more 
speculative  than  proven. 

The  parathyroids  are  formed  as  epithelial  outgrowths 
from  the  third  and  fourth  branchial  clefts;  the  lower 
parathyroid  (parathyroid  III.)  lies  sometimes  in 
contact  with  the  lower  pole  of  the  thyroid,  or  some- 
times farther  away,  as  low  down  as  the  thymus 
(Schafer),  while  the  upper  parathyroid  (parathyroid 
IV.)  is  usually  in  contact  with  the  upper  border  of  the 
thyroid  near  the  dorsal  aspect.  From  the  fact  that,  in 
many  animals,  the  upper  parathyroid  is  embedded  in 
the  substance  of  the  thyroid,  the  name  "  internal  " 
parathyroid  has  been  given  to  it,  the  lower  parathyroid 
being  known  as  the  "  external  "  parathyroid. 

MacCullum  came  to  the  conclusion  that  they  con- 
trolled in  some  way  the  calcium  metabolism  of  the 
body.     Calcium  moderates  the  activity  of  nerve  cells; 


46     THE  OEGANS  OF  INTERNAL  SECRETION 

therefore,  when  the  secretion  of  the  parathyroids  is 
deficient,  and  calcium  is  lost  from  the  nerve  cells, 
the  patient  will  suffer  from  an  exaggeration  of  nervous 
excitability.  This  corresponds  to  the  surmises  as  to 
the  causation  of  the  nervous  symptoms  which  are 
manifest  when  the  thyroid  has  been  extirpated.  In 
support  of  this  view,  the  administration  of  extracts 
of  the  parathyroid  glands  in  cases  of  tetany  has  been 
proved  to  be  efficacious  in  controlling  the  convulsions. 
It  will  be  remembered  that  tetany  is  a  prominent 
symptom  after  extirpation  operations  in  animals. 
Likewise  the  administration  of  calcium  salts  will 
control  the  symptoms  of  tetany. 

Opposed  to  the  views  just  quoted,  some  observers 
believe  that  the  parathyroids  are  portions  of  the  true 
thyroid  gland;  that  they  have  become  separated  from 
the  gland  itself,  or  that  they  secrete  the  same  colloid, 
although  they  have  not  as  yet  formed  vesicles;  or 
that  they  develop  into  normal  thyroid  tissue,  inter- 
mediate types  having  been  noticed. 

It  is  stated  that  if  all  four  parathyroids  are  removed 
the  animal  succumbs  rapidly,  no  matter  whether  the 
thyroid  is  left  intact  or  not.  If  one  parathyroid  be 
left,  death  does  not  usually  ensue,  although  tetany 
may  be  brought  on.  It  has  also  been  said  that 
changes  in  these  glands  are  very  common  in  cases 
of  tetany  in  children,  in  pregnant  women,  and  in 
osteomalacia  (a  disease  associated  with  defective 
calcium  metabolism).  This  would  seem  to  be  sup- 
ported by  the  beneficial  effects  of  calcium  administered 


THYEOID  AND  PARATHYROID  GLANDS    47 

by  the  mouth,  as  it  would  tend  to  replace  the  excessive 
loss  of  calcium  due  to  the  defective  parathyroid 
secretion. 

With  the  few  facts  at  our  disposal,  and  the  many 
speculative  theories  based  thereon,  it  is  natural  that 
many  diseases  should  have  been  attributed  to  an 
abnormality  of  these  glands.  To  take  one  example, 
it  has  been  suggested  that  paralysis  agitans  may  be 
due  to  disease  of  the  parathyroid  glands,  but,  un- 
fortunately, it  does  not  appear  to  benefit  by  the 
exhibition  of  extracts  of  these  glands.*  This  is,  of 
course,  not  tantamount  to  a  refutation  of  this  theory, 
as  it  may  mean  that  the  extract  undergoes  changes 
during  its  passage  through  the  body  which  rob  it  of 
its  natural  properties,  so  that  it  is  unable  to  replace 
the  normal  secretion  which  should  be  delivered  into 
the  blood-stream.  The  only  instance  which,  so  far 
as  I  am  aware,  has  been  published  in  which  para- 
thyroid extract  appears  to  have  been  absolutely 
successful,  and  to  have  been,  if  one  may  use  the 
expression,  specific,  is  described  by  Hur.5t  in  the 
Practitioner  for  January,  1915,  in  an  article  on  the 
parathyroids.  Briefly,  this  case  was  a  man  of  middle 
age,  who  had  suffered  from  an  enlargement  of  the 
thyroid  gland,  and  had  undergone  an  operation  in 
which  the  greater  part  of  it  was  removed.  He  re- 
mained well  for  two  years,  and  then  suddenly  became 

*  An  interesting  case  ol  paralysis  agitans,  in  which  pro- 
gressive atrophy  of  the  globus  pallidus  was  found,  is  described 
in  the  Medical  Annual,  1918,  p.  404. 


48     THE  ORGANS  OF  INTERNAL  SECRETION 

very  restless,  tremulous,  and  developed  fibrillary 
tremors  and  other  signs  which  closely  resembled 
Graves'  disease.  His  hair  ceased  to  grow,  he  became 
impotent,  his  bowels  were  loose,  and  his  weight 
decreased  very  rapidly. 

No  treatment  was  of  much  avail,  and  the  administra- 
tion of  dry  thyroid  gland  aggravated  the  symptoms. 
He  was  given  dry  ox  parathyroid  by  the  mouth,  and 
from  that  day  he  began  to  improve,  became  stronger? 
increased  very  markedly  in  weight,  and  returned  to 
work.  Not  until  he  had  been  taking  the  parathyroid 
gland  for  six  months  did  his  sexual  powers  return. 
Hurst  thus  concludes  the  account  of  this  very  interest- 
ing case:  "  His  weight  in  February,  1914,  had  risen 
to  189  pounds;  he  felt  perfectly  well  and  strong,  and 
no  trace  of  nervousness  remained,  although  he  was 
working  very  hard." 

Here,  apparently,  was  a  case  in  which  the  secretion 
of  the  parathyroids  was  deficient,  and  where  its 
administration  by  the  mouth  was  able  to  replace  the 
normal  secretion. 

If  this  latter  surmise  be  correct,  it  would  seem  that 
it  is  possible  for  an  analogous  treatment  to  that  of 
myxcedema  to  be  initiated,  if  only  we  could  arrive 
at  an  accurate  diagnosis.  It  would  support  the 
school  which  believes  in  the  separate  functioning  of 
the  thyroid  and  parathyroid,  and  might  eventually 
show  us  where  we  are  lacking  in  the  treatment  of 
exophthalmic  goitre.  It  is  certain  that  the  removal 
of  part   of  the   thyroid   does  not   cure  this   disease, 


THYROID  AND  PARATHYROID  GLANDS    49 

although  it  may  ameliorate  the  symptoms  for  a  variable 
time.  If  the  nervous  symptoms  are  due  to  excess  of 
thyroid  secretion,  then  removal  of  part  of  the  gland 
should  counteract  the  excess.  But  if  this  group  of 
the  many  symptoms  of  Graves'  disease  owes  its  exist- 
ence to  an  abnormality  of  the  parathyroids,  we  must 
alter  our  surgical  treatment  of  this  disease. 

On  the  other  hand,  we  have  yet  to  study  the  views 
of  that  school  winch  has  returned  to  Gley's  original 
belief:  that  the  parathyroids  are  part  of  the  thyroid 
gland;  that  they  are  an  embryonic  and  partly  developed 
thyroid  tissue.  In  support  of  this  view,  it  is  stated 
that  post-operative  tetany  is  greatly  benefited  by 
administering  thyroid  gland  by  the  mouth,  and  that 
pure  parathyroid,  even  in  larger  amounts,  has  not 
given  the  same  results.  It  would  appear  from  this 
that  tetany  owes  its  origin  to  deficient  thyroid,  and 
not  necessarily  deficient  parathyroid,  although  the 
ordinary  sheep's  thyroid  gland  contains  parathyroid 
substance. 

This  school,  therefore,  regards  the  parathyroids 
as  part  of  the  thyroid,  and  not  separate  structures; 
their  function  would  be  similar,  and  it  follows  from 
this  hypothesis  that  the  diseases  which  have  been 
tentatively  attributed  to  the  parathyroids  (mainly 
on  account  of  the  similarity  which  their  symptom- 
complexes  bear  to  those  produced  experimentally) 
must  in  reality  owe  their  origin  to  the  thyroid — 
assuming  that  they  are  in  any  way  connected  with  this 
gland.     This   is   comforting,   as   it   narrows   the   field 

4 


50     THE  ORGANS  OF  INTERNAL  SECRETION 

of  inquiry:  it  leaves  us  one  set  of  riddles  to  solve 
instead  of  two.  But  we  must  admit  that  this  view 
is  not  widely  accepted,  mainly  on  account  of  the  many 
small  facts  which  have  been  collecting,  albeit  slowly, 
to  show  us  that  the  parathyroids  are  undeserving  of 
neglect. 

Functions  of  the  Thyroid  Gland. 

We  must  now  leave  the  subject  of  the  parathyroid 
glands,  and,  before  concluding  this  chapter,  briefly 
review  the  theories  which  endeavour  to  account  for 
the  work  of  the  normal  thyroid  gland.  What  is  the 
function  of  the  thyroid  ?  Does  it  govern  metabol- 
ism ?  Is  it  a  "  vital  antiseptic  "  ?  Or  is  it  concerned 
with  growth  alone  ?  The  only  way  in  which  we  can 
attempt  an  answer  to  these  questions  is  to  give  some 
few  facts  and  more  theories  dealing  with  the  function 
of  this  gland. 

Firstly,  then,  the  thyroid  gland  possesses  the  peculiar 
property — peculiar  in  the  sense  that  it  is  not  shared, 
so  far  as  we  know,  by  the  other  endocrinic  glands — 
of  being  able  to  store  its  secretion.  This  is  proven  by 
the  fact  that,  in  cases  where  the  gland  has  atrophied 
or  been  removed,  its  secretion  can  be  replaced  by 
artificial  ingestion.  We  quite  naturally  turn  to  the 
colloid  as  being  the  stored-up  secretion,  and,  indeed, 
we  are  justified  in  so  doing,  as  there  is  evidence  to 
show  that  this  substance  arises  as  droplets  in  the 
epithelial  cells  lining  the  vesicles  (Dale).  Again, 
this    secretion   contains   a   relatively  large  percentage 


THYBOID  AND  PARATHYROID  GLANDS    51 

of  iodine  (0-2  per  cent.),  and  on  this  fact,  or  partly 
on  this  fact,  has  arisen  the  theory  that  the  thyroid  has 
a  phagocytic  or  antitoxic  action.  In  young  animals, 
however,  the  iodine-content  is  very  small,  and  in 
adult  animals  it  appears  to  bear  a  direct  ratio  to  the 
iodine-content  of  the  food.  On  the  other  hand,  there 
is  no  reason  to  suppose  that  the  power  of  the  body  to 
resist  intoxication  is  raised  when  iodine  or  the  iodides 
are  given  by  the  mouth;  although  Hunt  found  that 
young  thyroids  had  some  power  to  raise  the  resistance 
to  a  particular  substance  (acetonitrile),  and  that  this 
power  ran  more  or  less  roughly  parallel  to  the  iodine- 
content. 

In  this  connection,  the  action  of  iodides  upon  gum- 
mata  is  of  interest;  and,  as  pointed  out  by  Rendle 
Short,  the  beneficial  action  of  these  drugs  is  in  reality 
due  to  the  increased  action  of  the  thyroid  which  is 
engendered  by  the  administration.  He  says:  "  I  have 
found  thyroid  extract  quite  as  effectual  as  iodide  of 
potassium  in  healing  tertiary  syphilitic  ulcers."  In 
speaking  of  the  action  of  iodides  on  gummata  and 
atheroma,  he  says:  "In  cases  of  myxcedema  arterio- 
sclerosis is  early  and  intense.  The  same  is  true  in 
animals  after  removal  of  the  thyroid."1  Eiselsberg 
gives  a  number  of  very  convincing  photographs  of 
intense  atheroma  of  the  aorta  in  his  cretin  lambs  in 
which  the  thyroid  had  been  removed  in  early  life. 
In  the  second  place,  thyroid  extract  has  a  wonderful 
power  over  young  connective  tissue,  as  is  seen  by  the 
way  in  which  it  absorbs  the  subcutaneous  thickening 


52   THE  OEGANS  OF  INTERNAL  SECRETION 

of  myxcedema  and  cretinism.  It  is  not  surprising, 
therefore,  that  it  should  be  able  to  deal  also  with 
gurnmata  and  atheroma. 

The  theory  of  toxin-neutralization  states  that  the 
secretion  of  the  thyroid  has  the  power  to  neutralize 
toxins  which  find  their  way  into  the  blood-stream.  It 
goes  on  to  maintain  that  these  toxins  (of  albuminoid 
nature)  are  absorbed  from  the  alimentary  canal,  and 
undergo  iodization  in  the  thyroid  by  means  of  its 
secretion.  It  will  be  remembered  that  Lane  maintains 
that  atrophy  of  the  thyroid  gland  is  one  of  the  features 
of  chronic  intestinal  stasis.  Is  this  the  result  of  over- 
work ?  Hardly,  for  overwork  produces  hypertrophy, 
not  atrophy;  and  yet,  if  the  symptoms  and  signs 
attributed  to  intestinal  stasis  owe  their  origin  to 
toxaemia,  and  the  thyroid  is  the  neutralize^  then  (to 
reconcile  the  two  theories)  the  thyroid  should  be 
enlarged,  not  atrophied.  In  other  words,  it  should  be 
overworked,  not  idle. 

On  the  other  hand,  it  is  possible  that  after  long- 
continued  toxaemia  the  secretion  of  the  thyroid  might 
be  used  up,  the  reservoir,  to  which  we  have  already 
likened  the  thyroid,  becoming  dry.  That  this  may 
be  so  is  supported  by  the  clinical  evidence  in  certain 
cases  where  the  administration  of  thyroid  extract,  in 
cases  of  intestinal  stasis,  materially  improves  the 
symptoms.  What  has  been  called  "  the  vital  anti- 
septic "  power  of  the  thyroid  may  show  itself  in  pro- 
tecting the  body  from  the  toxins  arising  in  the  portal 
area.     It  has  been  shown,  experimentally,  that  after 


THYROID  AND  PARATHYROID  GLANDS    58 

ligature  of  the  bile- ducts  the  thyroid  colloid  increases, 
and  there  is  evidence  to  show  that  the  itching  of 
jaundice  can  be  ameliorated  by  thyroid  extract.  The 
bile- salts  in  the  urine  gradually  diminished  under  this 
treatment,  and  when  the  treatment  was  stopped  they 
again  appeared,  to  disappear  as  soon  as  thyroid  was 
again  administered. 

This  evidence  is  of  great  importance  to  the  organo- 
therapeutist,  for  it  suggests  yet  another  way  in  which 
extract  of  thyroid  can  be  utilized.  One  of  the  most 
difficult  problems  which  confronts  the  clinician  to-day 
is  the  diagnosis  and  treatment  of  intestinal  stasis.  This 
subject  is  referred  to  in  Chapter  XIV.,  where  it  is  shown 
that  thyroid  extract  assists  in  defending  the  body  from 
toxaemia,  especially  that  in  which  the  liver  is  concerned. 

We  know,  however,  several  facts  of  importance 
about  the  thyroid  to  balance  this  tangle  of  theories. 
Firstly,  we  know  that  a  train  of  symptoms  follows  its 
deficiency  or  absence,  whether  produced  experimentally 
or  arising  spontaneously,  and  that  these  symptoms 
will  yield  to  thyroid  feeding.  The  results  of  an 
extirpation  operation  in  young  animals  differ  only 
slightly  from  the  condition  which  we  know  as  cretinism, 
while  the  adult  analogy  of  this  we  encounter  as 
myxcedema. 

Thyroid  is  therefore  concerned  with  the  growth  of 
bone,  with  the  development  of  the  body,  and  with  a 
normal  circulation.  It  has  been  suggested  that  the 
reason  why  the  colloid  is  scanty  in  the  young  is  that 
it  is  used  as  rapidly  as  it  can  be  manufactured  by 


54    THE  ORGANS  OF  INTERNAL  SECRETION 

the  gland.  As  we  shall  see  when  discussing  thyroid 
deficiency,  the  clinical  pictures  of  the  slighter  forms 
of  inadequacy  require  discrimination  to  discover,  and 
are  as  yet  not  sufficiently  definite  for  their  wide 
acceptance.  But  the  above  facts  lend  themselves  to 
further  investigation. 

Again,  in  the  adult,  there  can  now  be  little  doubt 
that  absence  or  diminution  of  the  secretion  produces, 
or  helps  to  produce,  a  condition  of  secondary  anaemia. 
Whether  this  argues  any  direct  connection  with  the 
haematopoietic  system,  we  are  unable  at  present  to 
say.  That  the  thyroid  is  a  direct  circulatory  stimulant 
there  can  be  little  doubt;  for  the  slow  pulse,  cold 
extremities,  sluggish  circulation,  and  deficient  action 
of  the  sweat  glands  in  submyxcedema,  are  very  well 
recognized. 

The  interaction  of  the  thyroid  with  the  other  duct- 
less glands  is  discussed  in  the  previous  chapter,  and  its 
relation  to  growth  and  metabolism  has  already  been 
referred  to. 

We  must  here  leave  the  discussion  of  the  thyroid 
and  its  small  neighbours,  realizing  only  too  well  that 
many  blanks  still  remain  to  be  filled  up,  which  further 
light  on  this  most  difficult  subject  can  alone  do.* 

Reference. 

1  The  Newer  Physiology  in  Surgical  and  General  Practice,  by 
A.  Rendle  Short,  third  edition,  pp.  82,  83. 

*  For  a  fuller  account  of  the  thyroid  gland,  the  reader  is 
referred  to  McCarrison's  work  (see  Bibliography  on  p.  341). 


CHAPTER  III 

EXOPHTHALMIC  GOITRE 

Synonyms:  Graves'  Disease;  Basedow's  Disease; 
Hyp  erthy  roi  dism . 

With  increasing  knowledge,  the  conception  of  this 
disease  has  become  a  much  more  difficult  matter 
than  when  it  was  regarded  as  being  solely  due  to  an 
over-action  of  the  thyroid  gland.  Modern  views  as 
to  the  pathology  of  Graves'  disease  would  have  us 
believe  that,  although  derangement  of  this  gland  is 
present  in  this  malady,  the  thyroid  is  not  the  sole 
organ  at  fault,  neither  is  a  hypersecretion  of  this  gland 
alone  responsible  for  the  symptoms. 

Definition. 

Let  us  for  a  moment  refer  to  some  definitions  of 
this  condition  which  have  been  current,  and  then 
compare  these  with  modern  views  as  to  the  etiology 
and  pathology.  In  one  textbook  of  medicine  we  meet 
the  following  definition :  "A  disease  characterized 
by  enlargement  of  the  thyroid,  exophthalmos,  in- 
creased action  of  the  heart,  tremor,  and  nervou3 
instability."1     Again:  "  The  four  classical  symptoms 

55 


56  THE  OEGANS  OF  INTERNAL  SECRETION 

of  Graves'  disease  are — A  staring  appearance  of  the 
eyes,  generally  spoken  of  as  exophthalmos,  though 
there  need  be  no  actual  protrusion  of  the  eyeballs; 
moderate  and  almost  symmetrical  enlargement  of  the 
thyroid  gland;  a  pulse-rate  between  120  and  180 
per  minute — usually  about  140  when  the  attack  is 
moderately  severe;  and  extreme  nervousness,  with 
fine  tremor  of  the  outstretched  fingers.  When  all 
these  symptoms  are  present  at  the  same  time,  there 
can  be  little  doubt  as  to  the  diagnosis,  but  very  often 
some  of  them  are  absent,  and  it  is  possible  for  tachy- 
cardia to  be  the  only  symptom  of  the  disease." 2 
"  There  are  three  prominent  symptoms:  Protrusion  of 
the  eyeballs,  enlargement  of  the  thyroid  gland,  and 
frequent  action  of  the  heart."3  "  We  are  accustomed 
to  recognize  three  cardinal  symptoms  in  this  disease — 
namely,  (1)  tachycardia,  (2)  goitre,  and  (3)  exophthal- 
mos; but  we  must  remember  that  these  are  not  the 
only  symptoms."4 

These  definitions  represent  the  general  views  which 
have  been  held  on  the  nature  of  the  disease  and  on  the 
most  constant  symptoms. 

The  condition  was  first  recognized  by  the  celebrated 
Dublin  physician  whose  name  it  now  bears  about  the 
year  1835,  although  Von  Basedow  in  1840  published 
a  paper  on  the  subject.  Consequently  the  disease  is 
in  Germany  and  some  other  parts  of  the  Continent 
still  referred  to  as  "  Basedowsche  Krankheit,"  or 
"  Von  Basedow's  disease."  However,  as  early  as 
1825   Caleb   Parry,   of   Bath,   drew   attention   to   the 


EXOPHTHALMIC  GOITKE  57 

condition,  and,  according  to  Osier,  to  him  belongs  the 
credit  of  first  describing  the  disease.  Many  of  the 
early  conceptions  of  the  malady  have,  in  the  fulness  of 
time,  given  place  to  views  which  have  been  promul- 
gated from  the  results  of  the  extensive  practical 
physiological  research  which  has  been  undertaken  in 
order  to  establish  the  causation  of  the  disease.  But 
it  was  recognized  then,  and  it  is  believed  now,  that 
emotional  strain  can  precipitate  the  disease.  Thus, 
Trousseau  refers  to  a  lady  who  was  suffering  great 
grief  at  the  death  of  her  father,  and  had  been  crying 
for  a  long  time;  she  "  suddenly  felt  her  eyes  swell 
and  lift  up  her  eyelids."  This  was  accompanied  by 
copious  epistaxis,  violent  palpitation,  and  throbbing 
and  enlargement  of  the  thyroid.  A  few  days  later 
the  nature  of  the  disease  was  recognized.  Again, 
Stokes  describes  the  case  of  a  man  who  developed 
the  disease  from  long-continued  bleeding  from  piles; 
and  many  other  records  show  that  the  etiology  of  the 
disease  was  universally  regarded  as  a  wide  one. 

From  the  early  thirties  of  the  last  century  the  nature 
of  the  condition  was  recognized,  but  it  is  only  com- 
paratively recently  that  the  diagnosis  has  been 
narrowed.  Thus,  it  will  be  seen,  from  the  definitions 
quoted  above,  that  it  is  not  necessary,  as  used  to  be 
thought,  for  all  the  classical  symptoms  to  be  present 
in  any  given  case.  Nevertheless,  there  is  one  symp- 
tom without  which,  as  Mackenzie  rightly  insists,  the 
condition  cannot  be  diagnosed,  and  that  i3  persistent 
tachycardia. 


58     THE  ORGANS  OF  INTERNAL  SECRETION 

So  we  come  down  to  this:  that  exophthalmic  goitre 
may,  and  in  the  opinion  of  many  observers  does, 
exist  without  the  exophthalmic  symptom.  It  is,  there- 
fore, somewhat  unfortunate  that  the  name  of  the 
disease  should  be  inseparably  connected  with  a  symp- 
tom which  is  by  no  means  constant.  But  we  cannot 
at  the  moment,  at  any  rate,  suggest  any  other  name 
which  is  free  from  objection.  As  we  shall  see  later 
the  modern  nomenclature  which  is  sometimes  used — 
namely,  "  hyperthyroidism  " — is  open  to  an  equally 
serious  objection,  as  it  implies  that  it  is  always  an 
over-action  of  the  thyroid  alone  which  is  responsible 
for  the  features  of  the  disease,  of  which  we  must 
reckon  proptosis,  when  present,  as  one.  Again,  it  has 
been  pointed  out  by  one  observer  that  this  latter  symp- 
tom is  significant  of  over-action,  not  of  the  thyroid, 
but  of  the  adrenals.6  Therefore,  hyperthyroidism 
is  a  no  more  suitable  label  for  the  disease  than  is 
exophthalmic  goitre.  Although  there  seems  to  be  an 
objection  to  utilizing  the  name  of  the  discoverer  of 
a  disease  to  designate  that   disease,*  in  the  present 

*  It  may  be  affirmed  that  this  mode  of  naming  a  disease  after 
its  discoverer  is  to  be  deprecated,  partly  on  account  of  the 
difference  of  opinion  as  to  whom  the  credit  of  the  discovery 
really  belongs,  and  partly  because  it  is,  perhaps,  an  unfortunate 
reward  for  the  happy  pioneer  in  the  particular  disease.  Again, 
if  a  disease  is  discovered  more  or  less  synchronously  by  different 
observers  in  different  countries,  a  nomenclature  is  adopted  which 
varies  with  the  different  countries,  and  this  all  leads  to  confusion. 
If  a  disease  is  called  by  its  most  distinctive  feature,  this  will 
probably  be  similar  in  different  languages,  so  where  such  a 
course  is  possible  it  is  certainly  to  be  preferred. 


EXOPHTHALMIC  GOITRE  59 

instance  it  would  seem,  for  the  moment  at  any  rate, 
to  be  the  most  satisfactory  way  to  designate  this 
malady.  "  Graves'  disease  "  has  the  merit  of  being 
non-committal  as  to  symptoms,  and  less  unwieldy 
than  many  of  the  other  names  by  which  the  disease 
has  been  known. 

In  the  majority  of  textbooks,  the  malady  under 
discussion  is  referred  to  as  "  exophthalmic  goitre," 
in  contradistinction  to  ordinary  goitre.  When  the 
swelling  in  the  neck,  if  present,  is  accompanied  by 
the  other  well-recognized  signs  of  Graves'  disease, 
such  as  persistent  tachycardia,  exophthalmos,  tremor, 
and  other  symptoms  and  signs  to  be  described  anon, 
then  we  diagnose  the  presence  of  this  disease  as 
opposed  to  simple  goitre. 

Etiology  and  Symptoms. 

Graves'  disease  (as  we  shall  call  the  malady  in  this 
book)  is  seen  more  commonly  in  the  female  sex  than 
in  the  male,  and  more  commonly  in  young  people  than 
in  elderly.  It  has  been  seen,  however,  in  an  infant 
only  two  and  a  half  years  of  age,  and  several  cases 
are  on  record  of  the  disease  occurring  in  children  of 
both  sexes.  Von  Graefe  stated  that  the  proportion 
of  females  to  males  was  6  to  1,  while  Eulenburg  said 
that  the  ratio  was  at  least  2  to  1.  Trousseau's  cases 
show  a  ratio  of  50  to  8,  Henoch's  23  to  4,  and  Prael's 
28  to  1.  Whatever  figures  we  study  there  is  plainly 
a   vast   preponderance   of  females   over   males.     The 


60    THE  OKGANS  OF  INTEENAL  SECBETION 

commonest  time  for  the  disease  to  develop  is  in  the 
decades  twenty  to  forty,  and  its  features  are  often 
made  manifest  at  critical  times  in  the  history  of  the 
patient,  such  as  puberty,  the  catamenia,  and  the 
menopause.  Indeed,  it  is  said  that  in  normal  persons 
of  the  female  sex  the  thyroid  is  liable  to  swell  and  to 
exhibit  increased  vascularity  at  these  times  and  during 
sexual  excitement. 

As  we  have  already  indicated,  there  can  be  little 
doubt  that,  certainly  in  individuals  prone  to  the 
disease  (by  this  I  mean  persons  who  exhibit  signs 
indicative  of  thyroid  instability),  a  mental  strain  or 
a  sudden  anxiety  seems  to  be  capable  of  precipitating 
the  disease.  Again,  there  is  a  sufficiency  of  evidence 
to  show  that  a  parenchymatous  goitre  can  develop 
into  an  exophthalmic  goitre,  given  suitable  opportuni- 
ties. The  symptom-complex  which  is  produced  by 
thyroid  feeding  on  a  large  scale  differs  in  many  details 
from  the  symptom-complex  of  this  disease,  so,  as 
Biedl  says,  we  must  regard  the  similarity  of  the  two 
pictures,  not  as  conclusive  evidence  that  the  thyroid 
is  the  organ  responsible  for  the  disease,  but  as  very 
strong  presumptive  evidence. 

The  evidence  includes  many  signs  suggestive  of  the 
involvement  of  the  adrenal  system  in  Graves'  disease, 
and  some  of  the  symptoms  are  readily  explicable  if  we 
believe  that  the  adrenal  system  and  the  thyroid  are 
together  responsible  for  the  disease.  Sajous  divides 
the  disorder  into  these  stages:  the  first,  or  sthenic 
stage,  "  Exophthalmic  goitre  is   due  to  over- activity 


EXOPHTHALMIC  GOITRE  61 

of  the  thyroid  and  adrenal  glands,  and  to  the  ex- 
aggerated tissue  oxidation  this  entails";  the  second, 
or  asthenic  stage,  due  to  "  exhaustion  and  functional 
insufficiency  of  the  thyroid  and  adrenal  glands,  as  a 
result  of  their  prolonged  over- activity  during  the 
sthenic  stage."  The  disease  when  fully  developed  he 
describes  as  follows:  "  Exophthalmic  goitre  is  a  con- 
stitutional disease  due  to  excessive  functional  activity 
of  the  thyro-parathyroid  apparatus,  and  to  the  resulting 
dilatation  of  all  arteries  which  the  excess  of  thyro-para- 
thyroid secretion  causes  by  producing  excessive  phos- 
phorus oxidation  (and  elimination  as  P->05)  in  all 
tissues,  including  the  vascular  muscles  and  the  de- 
pressor nerve."* 

There  is,  according  to  this  author  and  Chittenden, 
whom  he  quotes,  increased  phosphoric  acid  metabolism 
and  excretion  in  this  disorder,  and,  the  brain  and 
nervous  system  being  especially  rich  in  this  substance, 
its  loss  is  shown  by  nervous  symptoms — agitation, 
restlessness,  and  capriciousness.  This  disease  is,  as 
is  well  known,  characterized  by  the  peculiar  mental 
attitude  possessed  by  the  patient,  to  which  we  shall 
refer  later.  Some  authors,  indeed,  consider  that 
Graves'  disease  is,  in  essentials,  a  neurosis;  and  Stod- 
dart,  in  comparing  the  symptoms  of  anxiety  neurosis 
and  exophthalmic  goitre,  says:  "  The  two  conditions 
differ  only  by  one  symptom  or  at  the  most  two.  It 
is  therefore  obvious  that  they  are  very  closely  allied. 

*  "  Internal  Secretions  and  Principles  of  Medicine,"  p.  214 
et  seq. 


62    THE  OKGANS  OF  INTERNAL  SECRETION 

Although  we  are  forced  by  such  considerations  (and 
others  to  be  considered  later)  to  the  conclusion  that 
exophthalmic  goitre  is  a  special  variety  of  the  anxiety 
neurosis,  it  would  be  incorrect  to  regard  them  as 
identical;  the  above  remarks  are  merely  intended  to 
justify  the  classification  of  exophthalmic  goitre  as  a 
neurosis."* 

Nobody  who  has  seen  Graves'  disease  often  will 
doubt  the  striking  mental  changes  which  occur; 
whether  the  majority  of  observers  will  agree  to  its 
classification  as  a  neurosis  is  questionable.  The 
nervous  symptoms,  which  include  muscular  spasms, 
choreic  movements,  and  even  convulsions,  are  explained 
by  Sajous  as  being  due  to  "  undue  erethism  in  the 
cerebro-spinal  axis  and  the  peripheral  nerves,  and 
explain  the  excessive  excretion  of  P205."  There  is,  in 
fact,  an  increased  wear  and  tear  on  the  entire  system, 
so  that  those  patients  lose  weight,  the  temperature  is 
usually  raised,  and  in  some  cases  a  considerable  rise  of 
temperature  is  noted.  Sajous  attributes  the  exoph- 
thalmos to  vaso- dilation  of  depressor  origin;  St  ell  wag's 
sign  to  the  same  cause.  Tachycardia  is  partly  explained 
as  the  concomitant  of  the  febrile  state,  and  partly  as 
the  erethism  of  the  central  nervous  system  and  the 
nerves  themselves,  including  the  accelerator  nerve. 

The  facts  and  their  explanations  here  quoted  cer- 
tainly offer  an  easily  acceptable  guide  to  the  underlying 
pathology  of  Graves'  disease.  The  summary  of  these 
conclusions  is  that  exophthalmic  goitre  can  be  divided 

*  "  Mind  and  its  Disorders,"  third  edition,  p.  223. 


EXOPHTHALMIC  GOITKE  63 

into  stages,  according  to  the  degree  of  over-action  of 
the  thyroid  and  adrenal  systems;  that  one  or  other  of 
these  organs  is  at  a  given  stage  in  the  ascendant, 
and  according  to  which  it  is,  so  will  the  signs,  particu- 
larly those  referable  to  the  circulatory  system,  vary. 
The  two  stages  above  referred  to  may  lead  to  a  third 
— namely,  "asthenic  or  myxoedematous  state" — in 
which  there  is  exhaustion  of  both  the  thyroid  and  the 
adrenals. 

When  we  come  to  study  the  symptoms  of  Graves' 
disease,  we  see  three  or  four  definite  and  fairly  con- 
stant features,  and  a  multitude  of  smaller  and  some- 
what vaguer  signs.  There  can  be  little  doubt  that 
tachycardia  deserves  the  first  mention,  as  it  is  very 
constant,  and  may  be  looked  upon  as  a  fundamental 
sign  of  this  disease.  Indeed,  it  is  one  of  the  symptoms 
which  can  always  bo  produced  by  the  ingestion  of 
thyroid  extract;  and  there  must  be  very  few  cases  of 
undoubted  exophthalmic  goitre  which  do  not  show 
this  sign.  The  pulse  is  usually  rapid,  ranging  from 
100  to  140  or  more  per  minute.  The  pulse-wave  is  not 
always  thin;  indeed,  in  many  cases  a  full  and  bounding 
pulse  is  observed.  Again,  it  is  usually  regular,  but  the 
rate  increases  upon  very  slight  exertion. 

In  this  connection  it  is  interesting  to  refer  to  the 
theory  which  Eppinger  and  Hess  brought  forward. 
They  consider  that  the  symptoms  seen  in  Graves' 
disease  enable  us  to  divide  these  cases  into  two  groups. 
In  the  first  the  symptoms  of  sympathetic  excitement 
predominate,  and  these  they  describe  as  sympathetico- 


64     THE  ORGANS  OF  INTERNAL  SECRETION 

tonic;  while  the  second  group  is  described  as  vago- 
tonic, from  the  fact  that  the  symptoms  seem  to 
proceed  from  disorganization  of  the  autonomous 
system.  "  Falta,  Eppinger,  and  Rudinger,  assume  a 
polyvalency  of  the  thyroid  secretion,  and  they  regard 
the  hyperthyroidism  of  Graves'  disease  as  the  out- 
come of  a  simultaneous  though  probably  independent 
stimulation  of  both  the  sympathetic  and  autonomous 
nervous  systems."6 

There  seems  to  be  little  doubt  that  tachycardia  is 
only  one  of  the  many  symptoms  seen  in  this  disorder 
which  can  be  justly  attributed  to  the  sympathetic 
nervous  system.     We  shall  refer  to  these  later. 

The  symptom  which  merits  consideration  next  is 
the  local  enlargement  of  the  thyroid  gland.  Although 
not  so  constant  as  tachycardia,  it  is  nevertheless 
present  in  the  majority  of  cases  of  this  disease.  The 
thyroid  is  generally  moderately  enlarged,  the  right  side 
being  perhaps  more  so  than  the  left.  In  some  cases, 
however,  the  enlargement  is  scarcely  perceptible, 
while,  on  the  other  hand,  it  may  be  very  great.  In 
the  early  stages  the  gland  is  soft  and  elastic  from 
vascular  engorgement,  but  later  it  becomes  harder 
from  fibrous  hyperplasia. 

Histologically  the  gland  presents  a  picture  of  diffuse 
enlargement,  with  a  great  increase  in  the  vascular 
supply.  There  is  definite  new  formation  of  tissue, 
which  runs  hand  in  hand  with  certain  retrogressive 
processes,  notably  cell  desquamation.  Young  follicles 
are  seen  associated  with  older  cells,  and  in  the  latter 


EXOPHTHALMIC  GOITEE  65 

may  be  seen  breaking- down  processes.  As  a  rule  a 
thrill  can  be  detected,  certainly  in  the  larger  tumours, 
and  as  the  disease  progresses  the  thyroid  may  alter 
in  size,  diminishing  in  favourable  cases.  It  is  said 
that  the  histological  appearance  in  Graves'  disease 
is  typical,  and  Erdheim  maintains  that  the  young 
cell  formations  with  fat  granules  are  characteristic  of 
Graves'  disease. 

For  a  long  time  the  proptosis  was  looked  upon  as 
an  essential  feature  of  this  disease,  and  it  is  only 
recently  that  we  have  come  to  realize  that  it  is  by 
no  means  always  present.  Its  origin  or,  rather,  the 
changes  which  underlie  the  exophthalmos  are  still 
unknown.  It  has  been  suggested  that  it  is  due  to  a 
deposit  of  fat  behind  the  eyeballs;  to  a  venous  con- 
gestion in  the  posterior  part  of  the  orbit;  to  dilatation 
of  the  retrobulbar  arteries;  or  to  contraction  of  Miiller's 
muscle.  It  is  pointed  out  that  the  sympathetic  system 
is  largely  connected  with  the  symptoms  of  this  disease, 
and  that  a  disorganization  of  this  system  will  account 
for  many,  indeed  for  most,  of  the  features,  always 
excepting  the  changes  in  the  gland  itself.  On  this 
theory  it  is  much  more  probable  that  the  proptosis  is 
due  to  circulatory  changes  than  to  either  a  contraction 
of  Miiller's  muscle  or  a  deposit  of  fat  in  the  orbit. 

There  are  certain  classical  signs  which  one  is  ac- 
customed to  look  for  in  association  with  the  ex- 
ophthalmos, and  we  must  briefly  refer  to  these.  The 
widening  of  the  palpebral  fissure  gives  an  appearance 
of  great  protrusion  to  the  eyeball,  and  this  is  partly 

6 


66  THE  ORGANS  OF  INTERNAL  SECRETION 

due  to  the  retraction  of  the  upper  lid.  This  is  known 
as  Stellwag's  sign.  Although  the  eyeball  in  many- 
cases  appears  to  be  prominent,  it  is  in  reality  less  so 
than  it  appears,  on  account  of  the  uncovering  of  the 
eyeball  due  to  the  retraction  of  the  upper  lid.  There 
is  also  a  diminution  of  the  reflex  excitability  of  the 
eye,  so  that  there  is  less  irritation  of  the  globe  than 
would  otherwise  be  the  case.  Another  sign  in  con- 
nection with  the  lid  is  known  as  Von  Graefe's  sign, 
and  consists  in  a  lagging  of  the  upper  lid  behind  the 
globe  during  the  downward  descent  of  the  eye. 

Sometimes  there  is  an  insufficiency  of  the  internal 
recti  muscles  of  the  eye,  as  a  result  of  which  con- 
vergence of  the  eyes  in  near  vision  is  imperfect 
(Mobius).     Occasionally  blepharo-clonus  is  present. 

Tremor  is  another  constant  sign  of  Graves'  disease, 
and  is  quite  characteristic.  It  is  usually  very  fine, 
and  confined  to  the  hands,  although  occasionally  it 
is  seen  in  the  muscles  of  the  trunk,  so  that  by  laying 
a  hand  on  the  shoulder  or  trunk  the  observer  can  feel 
a  quiver  of  the  whole  body  (Oppenheim).  The  tremor 
of  this  disease  is  usually  excited  by  movement  or  by 
nervousness,  but  is  also  present  during  rest.  The  rate 
of  movement  is  somewhere  about  nine  per  second,  and 
can  best  be  seen  when  the  patient  extends  the  hands 
with  the  palms  downwards. 

Gatch  has  recently  been  investigating  a  test  for 
hyperthyroidism,  which  was  first  suggested  by  Goetsch. 
The  test  consists  in  the  injection  of  8  minims  of 
1/1000  solution   of   adrenalin   diluted  with   an  equal 


EXOPHTHALMIC  GOITKE  67 

quantity  of  sterile  water.  "  A  white  patch  surrounded 
by  a  red  areola  appears  immediately  at  the  site  of 
puncture.  After  thirty  minutes  the  white  central 
patch  assumes  a  bluish- grey  tint,  which  in  about 
two  hours  fades  from  the  centre,  and  gradually  colours 
the  periphery.  The  bluish-grey  areola  thus  formed 
persists  for  three  to  four  hours  if  the  test  is  positive 
and  a  definite  degree  of  hyperthyroidism  exists.  In 
normal  subjects  the  duration  of  the  greyish  areola  is 
ephemeral;  the  degree  of  hyperthyroidism  present  is 
measured  by  the  time  which  elapses  before  the  areola 
disappears.  Gatch  has  frequently  found  the  test 
negative  as  soon  as  fourteen  days  after  thyroidectomy, 
in  cases  where  the  reaction  had  previously  been 
strongly  positive."* 

Before  turning  to  the  discussion  of  the  menta 
changes  present  in  Graves'  disease,  there  remain  a 
few  less  constant  symptoms  and  signs  which  we  have 
to  mention.  These  may  be  classed  under  the  headings 
vasomotor,  secretory,  and  trophic.  The  subject  of 
Graves'  disease  is  very  liable  to  suffer  from  profuse 
perspiration;  indeed,  in  some  cases  this  amounts  to 
a  definite  hyperidrosis.  As  we  stated  in  the  previous 
chapter,  these  patients  feel  the  heat  greatly,  and 
naturally  this  symptom  is  worse  in  hot  weather. 
The  sweating  may  be  more  or  less  local,  or  it  may  be 
general.  One  point  of  interest  in  this  connection  is 
with  regard  to  the  electrical  resistance  of  the  skin  in 
cases  of   Graves'   disease.     Vigoroux  first   discovered 

*  Editorial,  Medical  Press,  April  7,  1920. 


68  THE  ORGANS  OF  INTERNAL  SECRETION 

that  in  patients  suffering  from  exophthalmic  goitre 
the  resistance  of  the  skin  to  electricity  was  diminished. 
This  is  now  generally  believed  to  be  due  to  the  undue 
moisture  of  the  skin  owing  to  the  increased  sweating. 

Flushing  of  the  skin,  quite  irregular  in  distribu- 
tion, erythemata  of  a  patchy  nature,  pigmentation — 
particularly  of  the  margins  of  the  lids  of  the  eyes,  and 
sometimes  almost  as  marked  as  that  seen  in  Addison's 
disease — are  all  phenomena  of  this  condition.  As  is 
well  known,  there  is  a  tendency  to  loose  evacuations 
of  the  bowels,  sometimes  to  actual  diarrhoea;  while 
the  secretion  of  urine  is  also  increased.  The  digestive 
system  is  often  upset,  and  attacks  of  sickness,  with 
bulimia,  or,  alternatively,  loss  of  appetite,  are  about 
equally  common. 

The  reflexes  are  often  altered — more  usually  in- 
creased, although  they  may  be  diminished,  or  even, 
in  rare  cases,  absent. 

Cases  are  occasionally  encountered  in  which  the 
symptoms  present  a  strange  combination  of  those 
seen  in  exophthalmic  goitre  and  those  characteristic 
of  thyroid  deficiency.  Thus,  patches  of  lipomatosis 
are  sometimes  met  with  in  a  typical  case  of  Graves' 
disease;  while  occasionally  the  condition  of  the  skin 
approximates  much  more  nearly  to  that  typical  of 
submyxcedema.  Leonard  Williams  believes  that  there 
is  often,  if  not  always,  a  combination  of  excess  and 
deficiency  in  this  disease.  Again,  some  of  the  symp- 
toms which  we  are  accustomed  to  regard  as  indicative 
of  disease  in  the  chromaffin  system,  such  as  pigmenta- 


EXOPHTHALMIC  GOITRE  69 

tion,  would  suggest  the  presence  of  a  combination  of 
thyroid  and  adrenal  disturbance;  and  we  have  already 
said  that  many  of  these  symptoms  are  more  suggestive 
of  adrenal  than  thyroid  disturbance.  The  point  to 
remember  is  that  the  symptoms  and  signs  will  vary 
according  to  the  stage  of  the  disease;  so  that  if  we 
encounter  a  case  in  the  earlier  or  sthenic  stage  we  shall 
find  signs  present  which  will  not  be  there  in  the  later 
stages.  This  point  helps  us  to  understand  those 
patients  who  present  some  signs  of  over-action  of  the 
thyroid,  and  synchronously  exhibit  indications  of 
hypothyroidism. 

But  as  important,  or  nearly  as  important,  as  the 
physical  symptoms  of  this  complaint  is  the  mental 
change  which  characterizes  exophthalmic  goitre.  The 
main  features  of  the  sufferer  from  this  disease  are  well 
known,  but  perhaps  a  brief  sketch  of  the  mental 
make-up  of  the  patient  may  be  useful.  Whatever 
is  the  agent  at  work  in  these  cases,  whether  the  dis- 
turbance is  originally  in  the  sympathetic  system,  or  to 
be  attributed  to  an  excess  of  thyroid  secretion  due  to 
a  cause  or  causes  unknown,  it  is  one  fraught  with 
evil  for  the  peace  of  mind  both  of  the  patient  and  her 
relatives.  From  being  gentle  and  docile,  it  may  be, 
she  changes  to  an  intractable,  selfish,  restless,  and 
inconsiderate  being.  The  medical  attendant  as  a 
rule  receives  the  full  benefit  of  this,  and  little  he 
can  do  is  right.  He  is  either  old-fashioned  when  he 
explains  that  the  reason  for  rest  in  bed,  for  example, 
is  to  avoid  straining  an  already  weakened  heart;  or 


70     THE  OEGANS  OF  INTERNAL  SECRETION 

an  ignoramus  if  he  insists  that  rest  combined  with 
hygienic  principles  offers  the  best  hope  for  alleviating 
the  disease.  If  he  suggests  trying  a  new  remedy,  he 
is  experimenting  with  her;  if  he  persists  with  the  old, 
he  is  a  "  stick-in-the-mud." 

Perhaps  the  saddest  of  the  changes  wrought  by  this 
disease  are  the  changes  for  the  worse  in  the  psyche, 
and  it  behoves  the  medical  man  to  be  very  tactful 
with  such  patients,  and  to  remember  that  the  mind 
is  the  victim  of  a  disordered  bodily  functioning  and 
is  no  more  to  blame  for  its  vagaries  than  the  victim  of, 
let  us  say,  puerperal  mania.* 

The  mental  symptoms  are,  like  the  physical,  capable 
of  entirely  clearing  up ;  but  even  so,  Leonard  Williams 
doubts  whether  the  individual  is  ever  quite  the  same 
again.  There  can  be  little  doubt  that  this  disease 
plays  havoc  with  the  patient's  character.  It  changes 
the  quiet  to  the  restless,  the  unselfish  to  the  self- 
centred,  and  the  amiable  to  the  perverse.  That  these 
patients  are  notoriously  difficult  to  treat  is  well  known ; 
that  they  make  the  treatment  of  their  condition 
doubly  difficult  by  their  attitude  to  what  i3  being 
done  for  them  is  almost  equally  well  realized  by  every- 
one connected  with  the  case  except  the  patient  herself. 

Apart  from  the  changes  in  character  which  we  have 
outlined,  more  serious  symptoms  are  seen  in  connec- 
tion with  Graves'  disease.  Apart  from  actual  insanity, 
such  as  melancholia,  mania,  hallucinatory  confusion, 

*  For  a  fuller  discussion  of  the  psycho-physical  disturbances 
of  Graves'  disease  see  Chapter  XI.,  p.  232. 


EXOPHTHALMIC  GOITEE  71 

and  obsessions,  there  are  the  minor  changes  which  are 
apt  to  lead  to  these  more  serious  psychoses.  Thus, 
the  patient  is  excitable,  wildly  restless,  sleepless,  and 
confused.  She  is  incapable  of  organized  thought,  of  suc- 
cessful memory,  or  of  attentive  control ;  while  her  general 
mental  habits  have  been  well  described  by  Reynolds 
as  "  mental  chorea."  It  is  quite  obvious  that  it  may  be 
but  a  short  step  from  this  stage  to  that  of  insanity. 

Needless  to  say,  fortunately  only  a  relatively  small 
percentage  passes  from  the  mentality  characteristic 
of  Graves'  disease  to  that  typical  of  insanity.  Never- 
theless, the  picture  we  have  drawn  of  the  mental 
condition  of  these  sufferers  is  not  exaggerated.  It  is 
true  that  in  many  diseases  which  the  physician  is 
called  upon  to  treat  to-day  the  patient's  worst  enemy 
is  himself;  and  in  no  disease  is  this  more  true  than 
in  exophthalmic  goitre.  Consequently,  it  is  no  rare 
occurrence  for  such  a  patient  to  pass  from  one  doctor 
to  another,  giving  no  one  a  fair  chance  to  improve  the 
patient's  condition.  This  is  the  analogue  in  the  mental 
apparatus  of  the  restlessness  in  the  physical  system 
which  prohibits  the  patient  from  resting,  which  is 
the  one  thing  most  to  be  desired.  Thus  is  her  tempera- 
ment at  the  time  her  worst  enemy,  and  it  is  this 
which  needs  treatment  quite  as  much  as  the  syndrome 
of  symptoms  which  we  have  been  discussing. 

Such,  then,  is  the  bare  outline  of  what  constitutes 
Graves'  disease.  What  is  the  prognosis,  and  what 
can  we  do  to  benefit  that  part  of  suffering  humanity 
afflicted  with  Graves'  disease  ? 


72    THE  ORGANS  OF  INTERNAL  SECRETION 

Prognosis. 

First  as  to  prognosis.  The  course  of  the  disease 
is  very  variable;  it  may  in  rare  cases  be  rapidly  fatal, 
or  it  may  linger  for  many  years,  sometimes  showing 
improvement,  at  other  times  retrogressing.  Mackenzie 
gives  the  mortality  at  approximately  25  per  cent. 
In  patients  who  eventually  recover,  there  is  often  a 
period  when  no  improvement  seems  to  take  place 
and  the  disease  seems  to  be  stationary.  Even  in 
these  cases  there  is  a  prolonged  convalescence,  and 
sometimes  years  afterwards  some  slight  trace  of  the 
disturbance  can  be  found. 

In  the  early  stages  the  malady  is  very  liable  to  be 
diagnosed  wrongly,  some  such  diagnosis  as  neurasthenia 
being  made.  This  probably  partly  accounts  for  the 
advances  which  this  disease  makes  in  the  early  stages, 
owing  to  a  misconception  of  the  nature  of  the  trouble. 
Also  the  prognosis  must  be  based  upon  the  length  oi 
duration  of  the  disease,  the  prominence  of  individual 
symptoms,  the  means  of  the  patient,  and,  last  but  by 
no  means  least,  the  degree  of  mental  abnormality 
which  exists. 

But,  speaking  generally,  patients  who  have  had  the 
disease  for  a  long  time,  especially  where  treatment 
has  been  of  little  avail,  are  not  the  most  hopeful  of 
subjects,  and  there  seems  little  reason  upon  which 
to  base  hopes  of  complete  recovery.  Indeed,  in  such 
cases  as  these  it  is  doubtful  whether  they  are  ever 
entirely  restored  to  the  status  quo  ante.     Although  it 


EXOPHTHALMIC  GOITKE  73 

is  usual  to  see  amelioration  of  the  symptoms,  even  a 
vanishing  of  the  proptosis,  or  at  least  a  diminution  of 
the  amount  of  protrusion  under  successful  treatment, 
such  patients  are  extremely  liable  to  relapse.  Their 
nervous  symptoms  recur  from  time  to  time;  indeed,  it 
would  seem  that  it  is  very  difficult  for  them  to  return 
to  the  successful  functioning  of  this  system  once 
Graves'  disease  has  developed. 

There  have,  however,  been  many  reports  of  recovery 
of  long  duration.  Cheadle  reports  recovery  lasting 
twenty  years;  while  Oppenheim  says  that,  in  one  case 
of  his,  recovery  lasted  "  for  twenty-seven  years,  in 
another  for  eighteen,  in  four  for  six  to  eight  years."7 
The  chief  difficulty  lies  in  keeping  up  the  faith  of  the 
patients,  in  exacting  obedience,  and  in  counteracting 
individual  symptoms. 

Sudden  death  has  taken  place  during  the  course  of 
this  disease,  and  when  we  remember  the  strain  upon 
the  circulation,  the  dilatation  of  the  heart,  and  the 
disorganization  of  the  neuro-musculature  of  this  organ, 
it  is  not  to  be  wondered  at.  Sometimes,  as  a  sequel 
to  this  malady,  atrophy  of  the  thyroid  may  take  place, 
with  resulting  myxcedema. 

Treatment. 

We  shall  have  to  refer  at  some  length  to  the  treat- 
ment of  this  malady,  for  it  necessitates  a  discussion 
of  methods  which  have  been  utilized  for  many  years, 
as  well  as  those  which  have  found  favour  recently. 


74    THE  ORGANS  OF  INTEENAL  SECRETION 

Modern  physiological  research  has  enlightened  us  upon 
many  points  in  this  connection,  and  some  of  these 
have  indicated  different  methods  of  treatment,  a  few 
of  which,  at  any  rate,  have  shown  signs  of  success. 

It  will  be  readily  understood  that  the  treatment  of 
Graves'  disease  is  no  easy  matter;  for  we  have  to 
contend  with  a  condition  the  underlying  pathology  of 
which  is  not  definite,  and  with  a  patient  whose  men- 
tality renders  curative  measures  more  difficult  than 
they  need  be.  As  we  shall  see  later  on,  the  various 
methods  recommended  range  from  local  applications 
to  the  thyroid  gland  to  psychological  treatment — 
i.e.,  psycho-analysis.  The  practising  physician  has, 
therefore,  to  consider  from  which  of  the  many  remedies 
we  shall  presently  enumerate  he  will  choose  his 
weapons.  At  this  point  we  shall  consider  the  general 
treatment,  and  at  the  close  of  this  chapter  will  be  found 
a  summary  of  the  methods  in  use. 

The  resemblance  between  a  neurosis  (in  this  sense 
a  functional  nervous  disorder)  and  many  of  the  symp- 
toms of  the  disease  under  discussion  has  already  been 
referred  to.  A  good  working  rule  in  the  initial  stage 
of  the  treatment  of  any  disorder — more  especially  one 
without  a  specific  treatment — is  to  remedy  any  abnor- 
malities present,  even  if  they  have  no  apparent  connec- 
tion with  the  disorder.  This  rule  is  a  particularly 
sound  one  to  follow  when  commencing  the  treatment 
of  a  disorder  such  as  neurasthenia,  and  equally  so  when 
first  initiating  the  treatment  of  exophthalmic  goitre. 

To  commence  with,  a  careful  scrutiny  may  reveal 


EXOPHTHALMIC  GOITRE  75 

signs  of  oral  sepsis  which,  even  if  secondary  to  toxaemia 
arising  elsewhere,  nevertheless  requires  treatment. 
There  may  be — in  the  present  writer's  experience 
there  frequently  are — indications  of  gastro-intestinal 
disturbances,  a  furred  tongue,  bad  breath,  offensive 
sweat,  sallow  skin,  and  local  disturbances  of  digestion. 
It  may  be  argued  that  these  are  an  integral  part  of  the 
disorder,  and  nothing  more  than  secondary  manifes- 
tations of  an  underlying  disturbance;  but  it  is  equally 
likely  that  the  toxins  generated  in  the  bowel  have 
disturbed  the  endocrine  balance  and  produced  the 
thyro-adrenal  disorganization  to  which  we  have  already 
referred. 

In  any  case  the  gastro-intestinal  condition,  whether 
it  be  primary  or  secondary,  requires  treatment,  and 
this  should  be  initiated  from  the  commencement. 

The  frequency  with  which  attacks  of  diarrhoea  are 
encountered  in  these  patients  and  the  ease  with  which 
disorders  of  digestion  are  produced  points  to  an 
abnormal  intestinal  condition.  The  presence  of  in- 
dicanuria  is  likewise  suggestive,  and  the  frequent  and 
progressive  loss  of  weight  is  a  further  proof  of  mal- 
assimilation.  A  form  of  diet  should  be  selected  care- 
fully, and  insisted  upon.  It  is  not  easy  to  lay  down 
definite  lines  of  diet,  but,  speaking  generally,  a  diet 
largely  composed  of  dairy  produce  and  fresh  vegetables 
and  fruit,  with  no  butcher's  meat  and  little  fish  or 
poultry,  will  be  found  to  suit  many  patients.*  It  may 
be  that  the  bacteriologist  can  help  the  clinician  here, 
*  See  footnote  to  p.  26. 


16     THE  OKGANS  OF  INTERNAL  SECRETION 

by  investigating  the  nature  and  character  of  the 
faeces;  and  there  would  certainly  seem  to  be  indications 
for  withholding  flesh  food,  where  the  adrenals  are  over- 
stimulated. 

Plenty  of  milk,  cream,  butter,  cream-cheese,  brown 
bread,  fresh  fruit,  salads,  and  uncooked  vegetables, 
form  a  pleasant,  nutritious  and  innocuous  diet.  If 
steps  are  taken  to  aid  digestion  and  to  disinfect 
the  intestine  (where  there  is  evidence  of  intestinal 
indigestion)  we  have  laid  down  a  basis  of  treat- 
ment upon  which  a  more  detailed  structure  can  be 
built. 

Another  point  upon  wrhich  emphasis  must  be  laid 
ab  initio  is  rest,  and,  as  we  know,  this  is  the  point 
usually  disputed  by  the  patient.  But  there  must  be 
no  weakening  on  the  part  of  the  physician,  for  so  long 
as  the  loss  of  weight  and  strength  is  progressive,  and 
the  tachycardia  is  in  evidence,  everything  must  be 
done  to  protect  the  patient  from  increasing  the  kata- 
bolism  and  further  hurrying  the  heart. 

The  present  writer  is  unable  to  dogmatize  about  the 
matter  to  which  reference  has  already  been  made — 
namely,  the  value  of  psycho-analysis  in  the  treatment 
of  Graves'  disease.  Of  one  thing  there  is  no  doubt, 
that  psychotherapy,  in  its  widest  sense,  is  of  inestim- 
able value  in  any  disease  where  the  symptoms  are 
largely  coloured  by  disordered  emotion;  and  the  one 
under  discussion  is  no  exception  to  the  rule.  But  we 
need  say  no  more  on  this  subject,  for  wre  are  all  familiar 
with  the  results  which  can  be  achieved  by  judicious 


EXOPHTHALMIC  GOITRE  77 

psychotherapy,   whatever  variety  of    disturbed   func- 
tioning is  concerned. 

Many  of  the  therapeutic  measures  in  use  for  this 
disease  are  obviously  secondary  in  importance  to  the 
main  points  just  detailed.  For  instance,  the  adminis- 
tration of  such  drugs  as  the  bromides,  belladonna, 
aspirin,  the  salicylates,  and  so  on,  are  purely  empirical 
in  their  conception,  and  cannot  do  more  than  alleviate. 
The  application  of  ointments  to  the  thyroid  gland,  and 
more  recently  of  the  X-rays,  is  nearer  a  physio- 
logical antidote.  But  these  measures,  and  indeed  the 
surgical  removal  of  part  of  this  gland,  can  hardly  be 
based  upon  sound  medical  reasoning,  unless  we  believe 
that  ebullition  of  the  thyroid  is  the  starting-point  of 
the  condition,  and  that  the  hyperadrenia  and  its 
sequelae  are  secondary.  We  have  already  seen  that  in 
cases  which  reach  the  third  or  exhaustion  stage  the 
thyroid  and  adrenals  are  drained,  and  the  condition  is 
then  one  of  hypo-adrenia  and  hypo-thyroidisrn.  Any 
attempt  to  regulate  the  internal  secretions  in  Graves' 
disease,  by  modifying  or  removing  some  of  the  secretion 
from  the  thyroid,  is  only  tackling  half  the  problem; 
and  although  it  may  be  necessary  to  check  some  of  the 
symptoms  in  certain  cases  by  methods  such  as  these, 
we  must  always  realize  that  in  reality  we  are  only  taking 
up  the  disorder  from  one  point,  and  that  this  must  neces- 
sarily be  so,  until  we  can  establish  that  the  thyroid  is 
the  fons  et  origo  mail.  So  long  as  there  is  evidence 
that  the  adrenals  are  over-active,  then  we  must  bear  this 
in  mind,  and  not  concentrate  solely  upon  the  thyroid. 


78    THE  ORGANS  OF  INTERNAL  SECRETION 

But  whatever  treatment  we  may  initiate — whether 
we  incline  to  the  old  practice  of  counteracting  the 
symptoms  by  controlling  the  exuberance  of  the  heart's 
action,  by  producing  adequate  sleep,  by  anointing  the 
thyroid  gland,  or  by  countless  other  small  attentions 
— one  factor  remains  constant,  and  that  is  the  insist- 
ence upon  sufficient  rest,  even  complete  rest  in  bed  in 
bad  cases.  The  application  of  the  principles  of  general 
hygiene  cannot  be  insisted  upon  too  firmly,  for  this 
should  be  the  bed-rock  upon  which  all  subsequent 
treatment  is  based.  The  difficulty  is  that  the  restless- 
ness which  these  patients  so  often  exhibit  makes  this 
stipulation  a  difficult  matter  to  enforce.  Nevertheless, 
it  is  not  so  much  a  matter  of  the  practice  of  medicine 
as  of  the  practice  of  common  sense  which  suggests 
this;  for  it  must  be  obvious  that  exertion,  particularly 
undue  exertion,  which  is  always  followed,  as  it  is  in 
this  disease,  by  an  increase  in  the  symptoms,  must  be 
wrong,  and  therefore  in  no  circumstances  to  be  con- 
sidered. When  tachycardia  is  present,  as  it  invariably 
isr  our  first  aim  must  be  to  reduce  the  work  of  the 
heart  to  a  minimum,  and  in  doing  this  to  reduce  the 
tachycardia.  Even  if  the  rate  of  the  heart's  action 
is  not  excessive,  the  patient  must  be  made  to  take 
periodic  rests  in  the  course  of  the  day.  She  should 
rise  late  and  retire  to  bed  early,  resting  after  meals, 
and  avoiding  hurry  and  perturbation.  Where  tachy- 
cardia is  a  marked  feature,  and  more  especially  where 
the  signs  of  general  debility  with  marked  loss  of  flesh 
are  evident,  complete  rest  in  bed  is  essential. 


EXOPHTHALMIC  GOITRE  79 

There  can  be  little  doubt,  moreover,  that  these 
patients  require  every  hygienic  advantage  which  can 
be  given  them.  Thus,  where  possible,  they  should 
reside  in  the  country  or  by  the  sea,  but  not  in  too 
bracing  a  place.  They  should  rest  in  the  open  air, 
lie  in  the  sun  for  the  greater  part  of  the  day,  and 
attempt  no  exercise  of  a  strenuous  nature. 

Although  we  have  suggested  that  vegetables  are 
suitable  where  intestinal  toxaemia  is  present,  it  has 
been  recommended  that  these  should  be  omitted  from 
the  diet  of  the  patient,  on  account  of  the  iodine  which 
they  contain.  In  this  connection  Eendle  Short  says: 
1  We  see  also  that  exophthalmic  goitre  is  due  to  hyper- 
secretion of  the  iodothyrin,  as  is  proved  by  the  artificial 
imitation  of  the  disease  by  excessive  thyroid  feeding, 
by  the  excess  of  iodine  present  in  the  colloid  in  Graves' 
disease,  and  by  the  character  of  the  histological 
changes.  Thus,  we  have  reason  to  expect  good  from 
partial  removal,  which  has  been  very  successful  in 
the  hands  of  Kocher,  the  Mayos,  and  others.  It 
would  be  reasonable  also  to  try  the  effect  of  iodine 
starvation  by  eliminating  vegetables  and  ordinary 
tap-water  from  the  dietary,  and  substituting  for  the 
latter  the  water  of  a  goitre  well.  It  is  well  known 
that  exophthalmic  goitre  and  parenchymatous  goitre 
show  a  sort  of  geographical  antagonism,  and  the  effect 
of  the  water  in  reducing  the  amount  of  iodine  for 
conversion  into  iodothyrin  would  be  valuable."8 

It  must  be  borne  in  mind  that  parenchymatous 
goitre  is  supposed  to  occur  owing  to  a  deficiency  of 


80  THE  ORGANS  OF  INTERNAL  SECRETION 

the  iodotbyrin,  so  that  the  thyroid  hypertrophies  in 
an  endeavour  to  supply  that  deficiency.  If,  therefore, 
there  is  little  of  this  element  in  the  thyroid  of  sufferers 
from  parenchymatous  goitres,  they  may  be  helped 
by  the  ingestion  of  vegetables.  The  water  of  the 
well-known  goitre  wells  is  supposed  to  produce  paren- 
chymatous goitres  by  containing  a  substance  which 
deprives  the  body  of  the  iodine  by  forming  a  combina- 
tion with  it.  In  an  effort  to  counterbalance  the 
diminished  output  of  iodine  the  gland  hypertrophies. 
On  this  assumption,  then,  it  is  recommended  to  try 
the  water  on  patients  suffering  from  exophthalmic 
goitre,  in  the  hope  that  the  unknown  substance  in 
the  water  will  utilize  some  of  the  excessive  secretion 
of  the  thyroid. 

Turning  now  from  the  consideration  of  the  general 
treatment  of  this  disease,  we  find  a  host  of  other 
remedies  which  have  from  time  to  time  been  recom- 
mended. Apart  from  symptomatic  remedies,  over 
the  consideration  of  which  we  shall  spend  but  little 
time,  we  have  before  us  a  choice  of  many  drugs,  both 
for.  internal  and  external  application.  Of  these, 
preference  seems  to  lie  with  belladonna,  aspirin,  the 
salicylates,  arsenic,  and  iron  salts  (where  indicated). 
As  we  have  already  said.  Graves'  disease  is  often 
associated  with  anaemia,  and  therefore  some  benefit 
may  be  expected  by  the  administration  of  these 
latter  salts. 

Of  cardiac  tonics,  some  authorities  prefer  strophan- 
tus,   while    others    recommend    digitalis    and    nux 


EXOPHTHALMIC  GOITRE  81 

vomica.  But  the  help  which  the  physician  may  expect 
from  these  drugs  is  strictly  limited  to  their  local 
action  upon  tachycardia. 

Leonard  Williams  has  reported  good  results  in 
several  cases  from  the  hypodermic  or  intramuscular 
injection  of  bile  salts.  The  rationale  of  this  treatment 
lies  in  the  fact  that  it  is  well  known  that  these  salts 
circulating  in  the  blood  produce  a  sedative  effect  on 
the  brain  and  a  slowing  of  the  pulse. 

Of  recent  years  more  and  more  stress  has  been  laid 
on  the  chance  of  finding  an  organo-therapeutic  com- 
pound which  will  help  to  neutralize  the  excessive 
action  of  the  thyroid.  Extracts  of  the  adrenals  have 
been  tried,  as  also  the  extracts  of  pituitary,  the  ovaries, 
the  parathyroids,  and  the  spleen.  Unfortunately, 
these  have  not  given  good  results,  only  the  para- 
thyroid holding  out  any  hope  in  this  direction. 

But  there  remain  several  external  remedies  to 
mention,  some  of  which  have  been  stated  to  give  really 
good  results  in  some  cases.  Of  these,  the  X-rays 
is  very  well  spoken  of  when  applied  to  the  exterior 
of  the  gland,  and  it  has  been  said  on  many  occasions 
to  have  limited  the  exuberant  activity  of  the  thyroid. 
In  the  Bradshaw  Lecture,9  Hector  MacKenzie  describes 
in  some  detail  the  treatment  of  Graves'  disease  by  the 
X-rays.  He  relates  a  case  of  this  disease  which,  under 
R  ntgen  therapy,  was  converted  into  a  typical  case 
of  myxcedema.  In  all,  thirty-six  treatments  were 
given,  extending  over  a  period  of  four  years.  MacKenzie 
considers  that  a  possible  reason  why  treatment   by 

6 


82    THE  ORGANS  OF  INTERNAL  SECRETION 

the  X-rays  has  not  up  to  the  present  yielded  better 
results  is  because  it  has  not  been  persevered  with  for 
sufficiently  long.  In  commenting  upon  this  case,  he 
says:  "  I  have  never  before  seen  such  a  complete 
disappearance  of  the  signs  and  symptoms  of  well- 
marked  exophthalmic  goitre  as  has  taken  place  in  the 
above  case.  I  think  one  is  justified  in  ascribing  the 
cure  to  the  prolonged  X-ray  treatment. 

M  My  present  views  on  X-ray  treatment  are:  It 
may  prove  to  be  far  the  best  means  of  treatment  at 
our  command.  It  must  be  applied  in  no  half-hearted 
way.  It  must  be  persevered  with,  and  in  many  cases 
continued  for  a  long  period.  It  is  most  likely  to 
prove  beneficial  in  cases  where  the  thyroid  enlargement 
is  moderate  and  the  patient  is  not  so  seriously  ill  as 
to  necessitate  confinement  to  bed.  I  think  it  may 
prove  valuable  in  bringing  about  a  retrogression 
of  the  remaining  thyroid  after  hemithyroidectomy. 
I  have  not  at  present  sufficient  evidence  to  speak  of 
its  usefulness  where  the  goitre  is  a  very  large  one. 
It  has  seemed  to  fail,  as  other  remedies  do,  in  cases 
of  a  severe  type  and  rapid  course.  The  trend  of 
present  experience  in  respect  of  X-ray  treatment  is 
decidedly  in  favour  of  its  further  trial." 

Again,  galvanism  and  faradism,  applied  either  to  the 
gland  itself  or  to  the  sympathetic  in  the  neck,  has 
been  tried,  sometimes  with  success.  Or  a  compress  of 
adrenalin  applied  to  the  goitre  is  a  help  in  some 
cases.  I  have  occasionally  had  good  results  in  some 
patients  from  the  application  of  a  mercury  ointment 


EXOPHTHALMIC  GOITRE  83 

to  the  thyroid.  A  small  portion  rubbed  in  every 
night,  associated  with  internal  treatment,  has  on  more 
than  one  occasion  resulted  in  an  amelioration  of  the 
symptoms. 

Again,  since  1884  preparations  have  been  manu- 
factured from  thyroidectomized  animals.  Of  these, 
the  more  important  are  "  antithyroids  "  (Mobius), 
"  hsemato-ethyroidine,"  and  "  thyroidectin."  Beebe 
has  evolved  a  method  of  treating  Graves'  disease  by 
an  antiserum  produced  by  the  inoculation  of  a  thyroid 
preparation  in  animals.10 

It  is  too  soon  to  speak  of  the  results  of  this  latter 
treatment,  but  its  value  is  said  to  have  been  proved 
in  a  large  number  of  cases. 

Of  other  organic  extracts,  favourable  results  have 
been  reported  following  the  exhibition  of  pituitary 
gland;  and  in  one  case  under  my  care  the  symptoms 
were  markedly  improved  following  several  months  of 
this  treatment.  Thymus  gland  has  been  utilized, 
either  in  the  form  of  sweetbread  or  as  tablets,  in  the 
former  \  to  3  ounces  daily,  in  the  latter  one  to  three 
5-grain  tablets. 

Some  observers,  notably  H.  Campbell,11  advocate 
the  administration  of  calcium  salts  to  patients  suffer- 
ing from  exophthalmic  goitre,  and  claim  better  results 
from  treatment  in  which  this  medication  is  included 
than  from  any  other  treatment. 

Many  authorities  speak  very  highly  of  the  beneficial 
effects  of  X-rays,  and  claim  that  treatment  by  this 
method  successfully  counteracts  the  over-action  of  the 


84    THE  ORGANS  OF  INTERNAL  SECRETION 

thyroid;  while  some  observers  maintain  that  the  X-rays 
should  always  be  administered  before  an  operation  is 
finally  decided  upon. 

With  regard  to  the  question  of  operative  interference, 
there  can  be  little  doubt  that  it  should  be  reserved 
for  the  grave  cases  only,  and  that  it  should  only  be 
performed  after  all  other  remedies  have  failed. 

The  medical  man  must  insist  upon  hygienic  principles 
as  a  sine  qua  non,  and  he,  as  well  as  the  patient,  must 
regard  the  disease  as  one  requiring  the  tacit  obedience 
which  is  given  to  the  orders  of  the  medical  man  in 
a  disease  such  as  pneumonia  or  typhoid.  If  this  is 
done,  the  patient  is  prevented  from  straining  an  already 
overworked  organ,  and  much  possible  mischief  may 
be  prevented. 

Summary. 

The  methods  of  treatment  may  be  classified  into 
three  groups. 

1.  General  Measures. 

These  include  the  removal  of  sepsis,  the  treatment 
of  gastro-intestinal  disorders,  the  choice  of  a  diet 
suitable  to  the  individual  patient,  and  the  insistence 
upon  rest. 

2.  Internal  Remedies. 

These  may  be  classed  under: 

(a)  Inorganic  drugs. 

(b)  Organic  preparations. 

(c)  Dietetic  regime. 


EXOPHTHALMIC  GOITRE  85 

The  inorganic  drugs  are  mainly  chosen  for  their 
symptomatic  action:  digitalis  for  its  slowing  action  on 
the  heart  and  its  diuretic  effect;  aspirin  as  a  sedative 
and  where  "  rheumatic  "  pains  are  a  trouble;  bella- 
donna, strychnine,  the  bromides,  etc.,  where  their  help 
can  be  utilized  to  lessen  a  symptom.  Of  the  organic 
remedies,  pituitary,  thymus,  and  the  preparations  from 
thyroidectomized  animals,  can  be  ordered;  but  adrenal 
substance  is  only  likely  to  be  helpful  in  the  later  stages 
where  there  is  adrenal  exhaustion. 

Dietetic  treatment  will  include  the  prohibition  of 
vegetables  and  tap- water,  the  omission  of  meat  from 
the  diet  in  toxic  cases  of  gastro-intestinal  origin,  and 
the  attempt  to  promote  assimilation  by  assisting  the 
digestive  functions. 


3.  External  Remedies. 

These  include: 

1.  Applications  to  the  thyroid  and  the  sympathetic. 

2.  Surgical  interference. 

Ointments  or  solutions  of  drugs  can  be  applied  to 
the  gland  in  the  hope  of  lessening  its  activity.  Mercury 
ointment,  adrenalin  solution,  the  X-rays,  and  gal- 
vanism to  the  cervical  sympathetic,  are  among  this 
group.  Surgical  treatment  includes  ligature  of  the 
superior  thyroid  arteries,  and  removal  of  one  lobe  of 
the  gland.  A  combination  of  these  methods  has  been 
recommended  by  some  surgeons. 


86    THE  OBGANS  OF  INTEENAL  SECRETION 

In  conclusion,  we  must  emphasize  the  fact  that,  of 
all  diseases  which  the  medical  man  is  called  upon  to 
treat,  probably  no  one  makes  such  calls  on  his  per- 
severance and  patience.  For  he  has  to  treat  an 
irresponsible  patient,  and  one  who  is  not  the  best 
judge  of  her  condition.  He  requires  infinite  tact  and 
an  everlasting  patience  if  he  is  to  see  the  fruits  of 
his  labours.  Furthermore,  he  must  perforce  try  any 
remedies  which  hold  out  a  chance  of  help,  and  he  must 
discriminate  nicely  between  those  which  are  logically 
futile  and  those  which  are  based  upon  reason. 

There  is  some  ground  for  hoping  that  in  the  near 
future,  as  our  knowledge  of  the  disease  and  its  causa- 
tion widens,  we  shall  evolve  a  more  satisfactory  mode 
of  treatment.  For  the  present  we  must  make  up  by  our 
resourcefulness  what  we  lack  in  our  nicety  of  knowledge. 

References. 

1  A  Textbook  of  Medical  Practice,  edited  by  Bain,  p.  315. 

2  Index  of  Differential  Diagnosis  of  Main  Symptoms,  edited 
by  French,  p.  772. 

3  The  Practice  of  Medicine,  by  Taylor,  p.  860. 

*  A  Textbook  of  Nervous  Diseases,  Oppenheim,  p.  1343. 
6  Maurice,  Lyon  Medical,  quoted  by  Leonard  Williams  in 
Practitioner,  January,  1915,  p.  96. 

6  The  Internal  Secretory  Organs,  by  Biedl,  p.  98. 

7  Oppenheim,  Textbook  of  Nervous  Diseases,  p.  1349. 

8  The  Newer  Physiology  in  Surgical  and  General  Practice,  by 
A.  Rendle  Short,  pp.  85,  86. 

9  Lancet,  1916,  ii.  815. 

10  The  Diseases  of  the  Ductless  Glands,  for  Practitioners  of 
Medicine  and  Surgery,  by  S.  P.  Beebe. 

11  H.  Campbell,  Exophthalmic  Goitre,  Clinical  Journal,  1915, 
xliv.  329. 


CHAPTEE  IV 

THYROID  DEFICIENCY 

In  the  previous  chapter  we  dealt  with  the  disease 
variously  known  as  "  Graves'  disease,"  "  exophthalmic 
goitre,"  and  "  hyperthyroidism,"  and  showed  that 
there  is  strong  evidence  to  support  the  view  that  the 
symptoms  are  largely  caused  by  excess  of  the  thyroid 
secretion.  In  this  chapter  we  propose  to  discuss 
thyroid  deficiency,  laying  emphasis  on  the  lesser 
degrees. 

The  history  of  thyroid-therapy  has  already  been 
given,  and  we  have  described  the  earlier  operations  of 
Kocher  upon  the  thyroid,  and  referred  to  the  condition 
of  "  cachexia  strumipriva  "  which  was  liable  to  ensue. 
Likewise  we  have  mentioned  the  earlier  work  upon  the 
functions  of  this  gland,  and  the  discovery  by  Gull 
and  Ord  of  the  disease  myxoedema.  Eeference  was 
also  made  to  the  important  fact  elicited  by  G.  R. 
Murray,  that  this  condition  yielded  to  the  adminis- 
tration of  extract  of  thyroid  gland. 

The  discovery  was  of  the  greatest  importance,  and 
for  two  reasons:  First,  because  it  proved  beyond 
question  that  the  peculiar  disease  to  which  the  name 
11  myxoedema  "  had  been  assigned  was  largely  due  to 

87 


88    THE  OEGANS  OF  INTERNAL  SECRETION 

a  deficiency  or  absence  of  the  thyroid  secretion; 
second,  and  even  more  important,  it  enabled  complete 
relief  to  be  afforded  to  the  unfortunate  sufferers. 

Since  that  time  a  great  deal  of  work  has  been  done 
on  the  thyroid,  both  by  laboratory  workers  and 
clinicians,  with  the  result  that  myxoedema  has  emerged 
from  the  nebulae  of  ignorance,  and  has  taken  its  place 
as  a  curable  disease. 

But  quite  recently  workers  in  all  fields  of  medicine 
have  been  observing  cases  which,  while  they  were  by 
no  means  comparable  to  myxoedema,  were  sufficiently 
similar  to  appear  to  resemble  this  condition  in  certain 
points.  As  a  countenance  reminds  one  of  a  more 
familiar  face  by  reason  of  a  similarity  in  one  feature, 
so  do  these  cases,  sometimes  because  of  an  item  one 
can  barely  specify,  make  one  think  of  the  more  marked 
disorder. 

In  this  chapter,  then,  we  wish  to  include  those 
cases  whose  vagueness  is  a  defiance  to  conclusive 
diagnosis,  as  well  as  the  more  definite  disease  which 
has  received  the  name  of  "  myxoedema."  As  we 
have  already  in  a  previous  chapter  discussed  "  cachexia 
strumipriva,"  we  shall  here  confine  our  attention  to 
that  variety  which  arises  apparently  idiopathically, 
and  not  ensuing  after  operative  procedures. 

Myxoedema. 

We  will  briefly  review  the  features  of  this  condition, 
but  will  not  attempt  to  describe  them  in  any  detail,  as 
they  can  be  found  discussed  in  any  textbook  of  medicine. 


THYROID  DEFICIENCY  89 

As  we  have  already  said,  Gull  and  Ord,  G.  R.  Murray, 
Kocher,  Mayo,  and  others,  are  the  workers  responsible 
for  unearthing  the  cause  of  the  symptom-complex 
which  is  known  as  myxcadema,  and  to  Murray  belongs 
the  credit  of  discovering  that  the  administration  of 
thyroid  extract  relieved  the  symptoms. 

Myxcedema  is  one  of  those  interesting  clinical  con- 
ditions which  are  diagnosed  rather  by  the  summary 
of  the  effects  produced  by  the  individual  symptoms 
than  by  one  predominant  feature.  Thus,  we  find 
that  a  typical  instance  shows  to  the  observer  a  slowly- 
moving,  mentally  sluggish,  and  prematurely  aged 
individual,  with  localized  deposits  of  fat,  more  marked 
in  certain  areas,  a  dry,  rough  skin,  characteristic 
facies,  and  uncertain  gait.  The  patient  is  altered  in 
most  ways ;  indeed,  the  disease,  in  common  with  many, 
if  not  most,  of  the  serious  disturbances  of  the  endo- 
crinous glands,  changes  the  personality  of  the  patient 
almost  beyond  recognition;  but  this  alteration  is,  in 
the  majority  of  cases,  gradual. 

The  onset  of  the  disease  is  insidious,  and  may 
occupy  several  years,  although  in  a  few  instances 
its  onset  is  more  acute.  The  initial  symptoms  vary 
in  different  cases,  but  most  usually  commence  with 
lassitude,  debility,  disinclination  for  exertion,  and 
marked  susceptibility  to  cold  and  chills. 

The  patient  appears  a  changed  man,  and,  to  anyone 
who  has  not  seen  Mm  for  a  protracted  period,  almost 
a  different  being.  He  becomes  much  stouter,  and 
the  actual   body-weight  is  increased,   but  the  fat  is 


90    THE  ORGANS  OF  INTERNAL  SECRETION 

deposited  in  a  characteristic  manner.  Pads  of  adipose 
tissue  are  situated  in  the  clavicular  regions,  over  the 
cervical  spinal  area,  and  in  the  neighbourhood  of 
the  lower  ribs  and  flanks.  But  perhaps  the  facies  is 
even  more  characteristic.  The  evelids  are  thickened, 
with  resilient  bags  of  fluid  under  the  lower  lids;  the 
lips,  ears,  and  tongue,  are  enlarged;  and  the  whole 
appearance  of  the  face  is  one  of  extreme  coarseness. 
At  the  same  time  there  is  an  absolute  lack  of  any 
intelligent  expression  in  the  face;  the  features  are 
immobile,  with,  in  some  cases,  a  slight  expression  of  sur- 
prise, owing  to  the  eyebrows  being  somewhat  raised.* 

The  skin  loses  its  normal  moisture,  and  becomes 
harsh,  dry,  and  rough.  The  teeth  are  frequently  in 
a  state  of  decay,  the  nails  are  ridged,  and  the  hair 
loses  its  gloss  and  shows  evidence  of  trophic  change — 
in  fact,  the  epidermal  appendages  undergo  atrophic 
degeneration. 

The  individual  becomes  comparatively  lifeless. 
His  extremities  change;  his  hands  are  carried  in  a 
peculiar  manner,  which  has  received  the  name  of 
"  spade-hands,"  while  his  feet  enlarge  (not,  however, 
in  a  marked  manner,  as  is  seen  in  gigantism),  and  are 
carried  in  a  clumsy  manner.  Even  the  ringers  show 
a  change,  for  they  are  shaped  somewhat  like  sausages, 
and  are  not  narrower  between  the  joints  as  are  the 
fingers  of  a  normal  person. 

*  In  "  The  Expression  of  the  Emotions,"  Darwin  draws 
attention  to  the  curious  fact  that  cretins  never  weep.  They 
may  cry  out  or  moan,  but  do  not,  it  appears,  shed  tears. 


THYROID  DEFICIENCY  91 

Small  warty  growths  are  liable  to  appear  on  the 
surface  of  the  skin;  while  patches  of  dry  eczema, 
similar  to  psoriasis,  make  their  appearance. 

The  changes  in  the  habits  are  equally  characteristic. 
The  speech  is  slow,  and  a  long  time  elapses  before 
an  answer  is  given  to  a  question.  Co-ordination  is 
interfered  with,  and  the  gait  is  "  waddling."  The 
mental  attitude  is  almost  exactly  antagonistic  to  that 
which  is  typical  of  exophthalmic  goitre.  Thus,  the 
patient  is  slow  in  every  act,  whether  this  act  involves 
mental  or  bodily  exertion.  The  finer  co-ordinations 
of  the  muscles  are  deficient,  a  greater  length  of  time 
is  required  even  for  simple  acts,  while  the  mental 
hebetude  is  shown  by  the  set  and  unintelligent  ex- 
pression of  the  face. 

This  disease  depends  upon  an  atrophy  of  the  thyroid 
gland,  which  can  be  demonstrated  by  an  examination 
of  the  gland  in  the  neck.  It  will  be  much  harder  to 
localize  than  in  health,  and  to  the  examining  finger 
its  presence  can  only  be  detected  by  requesting  the 
patient  to  swallow. 

That  the  disease  owes  its  origin  to  an  absence  or 
diminution  of  the  thyroid  secretion  there  can  be  no 
doubt;  for  the  administration  of  an  extract  of  this 
gland  removes,  or  markedly  lessens,  the  symptoms. 


Lesser  Degrees  o!  Hypothyroidism. 

Now  let  us  turn  for  a  moment  to  the  study  of  the 
lesser  degrees  of  deficiency  in  thyroid   output,   and 


92  THE  OEGANS  OF  INTEENAL  SECEETION 

we  will  then  consider  the  physiological  effects  which 
the  thyroid  produces  upon  the  body. 

Needless  to  say,  it  is  a  more  difficult  matter  to  deal 
with  these  lesser  degrees  than  it  is  to  diagnose  those 
marked  instances  known  as  myxoedema.  There  can 
hardly  be  any  mistaking  a  case  of  myxoedema,  unless 
a  particular  instance  is  very  atypical.  Once  a  typical 
instance  is  seen,  the  peculiar  characteristics  cannot 
well  be  forgotten.  When,  however,  we  come  to 
describe  the  symptoms  and  signs  which  would  lead  us 
to  arrive  at  a  diagnosis  of  hypothyroidism,  the  diffi- 
culty arises  that  the  various  signs  are  widely  divergent 
(according  to  modern  views),  and  that  their  presence 
at  all  may  be  transitory,  or,  again,  the  physical  signs 
may  be  very  few.  We  shall  endeavour  to  describe 
those  signs  which  are  usually  present  in  a  case  of  sub- 
myxcedema,  laying  especial  emphasis  upon  those 
which  are  characteristic.  In  this  way  it  is  hoped  that 
those  cases  requiring  thyroid  medication  will  be  more 
readily  recognized. 

As  is  to  be  expected,  on  the  whole  the  clinical 
picture  is  a  modified  version  of  myxoedema,  with  this 
difference,  that  the  disease — i.e.,  the  thyroid  deficiency 
— is  still  probably  in  its  youth,  and  the  more  advanced 
changes,  which  are  dependent  upon  structural  alter- 
ations of  the  grosser  kind,  are  absent. 

It  is  not  possible  with  our  present  knowledge  of 
this  subject  to  do  more  than  hazard  a  guess  as  to  the 
cause  of  thyroid  insufficiency,  and  this  we  have  already 
done.1    Whether  prolonged  illness  on  the  physical  side, 


THYROID  DEFICIENCY  93 

and  anxiety  on  the  mental,  are  capable  of  initiating 
a  thyroid  disturbance  we  do  not  know  for  certain. 
With  the  evidence  at  our  disposal,  it  would  seem 
probable;  for,  in  the  experience  of  most  medical  men, 
hypothyroidism  is  more  liable  to  ensue  after  illness, 
worry,  and  similar  harmful  processes,  than  it  is  to 
arise  spontaneously.*  Whatever  its  genesis,  it  be- 
hoves the  medical  man  to  be  on  the  lookout  for  its 
signs,  more  especially  after  acute  illness.  Let  us 
briefly  review  its  features,  and  outline  the  signs  of 
thyroid  insufficiency.  Before  doing  this,  however,  it 
it  better  to  state  that  there  is  a  certain  difference  of 
opinion  as  to  what  constitutes  the  typical  picture 
of  thyroid  insufficiency.  We  shall,  therefore,  at  this 
place  confine  our  remarks  to  those  signs  about  which 
there  can  be  little  dispute,  and  in  conclusion  we  shall 

*  I  described  a  case  of  submyxoedema  in  a  young  male  subject 
in  the  British  Medical  Journal  for  June  20,  1914.  Thi3  followed 
a  prolonged  period  of  financial  stress  on  the  Stock  Exchange, 
and  was  quite  typical  in  its  features.  The  patient  was  a  young 
man,  who  had  been  out  of  sorts  for  some  weeks,  and  had  gone 
about  his  usual  occupations,  although  he  had  noticed  that  he  had 
been  putting  on  weight  rapidly.  Briefly,  his  symptoms  con- 
sisted in  dyspnoea  on  exertion,  bradycardia,  eczematous  rashes, 
pads  of  fat  in  the  clavicular  region,  subnormal  temperature, 
slow  pulse,  and  trophic  changes  in  the  hair.  Even  the  "  eye- 
brow "  sign  was  present.  This  man  was  first  treated  with 
cardiac  stimulants,  rest,  and  general  hygienic  measures,  but 
made  no  progress.  The  day  after  he  commenced  thyroid 
medication  the  temperature  approximated  to  the  normal,  the 
pulse-rate  increased,  he  became  more  comfortable  in  himself, 
and  after  three  weeks'  treatment  his  good  health  was  restored, 
with  a  reduction  of  weight.  As  may  be  imagined,  his  tem- 
perature chart  was  most  instructive. 


94  THE  OEGANS  OF  INTERNAL  SECRETION 

discuss  the   many   points  in   this   connection    about 
which  opinion  is  unsettled. 


Signs  of  Thyroid  Insufficiency. 

When  studying  the  main  features  of  Graves'  disease, 
we  saw  that  the  rate  of  bodily  metabolism  was  vastly 
increased,  that  the  nutritive  exchanges  were  acceler- 
ated, and  that  there  was  a  loss  of  weight  in  consequence. 
Again,  we  noted  that  the  vasomotor  system  was 
irritable,  that  perspiration  was  easily  induced,  erythe- 
rnata  were  frequent,  and  that  the  tendency  to  the 
production  of  glycosuria  was  increased.  The  general 
picture  of  thyroid  insufficiency  is  exactly  opposite 
(I  am  speaking  of  the  main  features)  to  that  seen  in 
exophthalmic  goitre.  Let  us  take  the  salient  points 
one  by  one: 

Temperature. — In  this  condition  the  bodily  tempera- 
ture is  usually  subnormal,  in  extreme  cases  as  low  as 
96°  P.,  more  generally  about  97°  to  97-5°  or  98°  F.  In 
any  case,  if  the  temperature  be  taken  consistently,  it 
will  rarely  be  found  to  be  normal.  In  this  connection 
we  must  remember  that  these  patients  feel  the  cold 
in  a  marked  manner,  and  are  in  a  more  or  less  constant 
state  of  chilliness.  A  patient  who  constantly  com- 
plains of  his  "  bad  circulation  "  should  be  suspected 
of  thyroid  inadequacy. 

Pulse. — The  pulse-rate  in  submyxcedema  is  con- 
sistently slow,  although  I  am  aware  that  many  authori- 
ties differ  from  this.     I  would  therefore  modify  this 


THYROID  DEFICIENCY  95 

statement  by  saying  that,  where  other  signs  of  thyroid 
insufficiency  are  present,  and  the  pulse-rate  is  not 
slower  than  normal,  or  even  faster,  this  is  a  sign  that 
the  condition  present  is  not  one  of  simple  thyroid 
inadequacy,  but  is  a  condition  of  complicated  endo- 
crinous disturbance — a  condition  in  which  there  may 
be  more  or  less  concomitant  disturbance  of  the  thyroid 
and  some  other  internal  secretion,  or  in  which  there 
may  be  a  concurrent  hypo-  and  hyper-thyroidism. 

General  Nutrition. — In  submyxoedema,  just  as  in  the 
larger  disease,  there  is  a  storage  of  products  of  diges- 
tion, as  is  seen  by  the  larger  amounts  of  sugar  which 
can  be  consumed  before  glycosuria  is  produced.  The 
bodily  weight  is  therefore  increased,  but  the  deposit 
of  fat  is  more  or  less  local,  as  in  myxcedema,  and  certain 
areas  are  more  affected  than  others.  Thus,  the  neck 
and  shoulders  are  thickened,  the  clavicular  regions 
contain  pads  of  fat,  while  the  feet  and  hands,  ankles 
and  thighs,  are  often  found  to  be  unaffected.  Again, 
the  hypochondrium  is  another  situation  which  in- 
creases in  size,  while  the  abdominal  wall  frequently 
contains  masses  of  fat.*  A  sudden  increase  of  weight, 
without  obvious  cause,  should  make  us  at  once  suspect 
some  thyroid  disturbance. 

*  The  condition  known  as  "  chronic  subcutaneous  fibrosis," 
about  •which  Stockman  of  Glasgow  has  written,  although  not 
attributed  to  deficient  thyroid  secretion,  nevertheless  yields  to 
the  ingestion  of  thyroid  extract.  This  condition  is  characterized 
by  the  increase  of  fat,  but  in  the  subcutaneous  tissue  are  also 
found  masses  of  fibrous  tissue,  and  the  latter  tissue  in  this 
complaint  is  very  tender  to  the  touch. 


96  THE  OEGANS  OF  INTERNAL  SECRETION 

Skin. — The  skin  is  dry,  rough,  patchy  in  places,  and 
may  be  in  an  eczematous  condition.  The  internal 
surfaces  of  the  tibiae,  the  sternum,  the  forearm,  and 
the  back,  are  the  main  situations  where  ichthyotic 
rashes  are  seen.  There  is  usually  present  in  thyroid 
insufficiency  an  itching,  which  is  sometimes  so  intoler- 
able as  to  make  the  patient  wish  to  scratch  every  part 
of  his  body  at  the  same  time.  There  may,  on  the  other 
hand,  be  little  or  nothing  to  see,  but  the  proof  that 
the  skin  irritation  is  due  to  the  diminution  of  thyroid 
secretion  is  that  it  gradually  yields  when  thyroid 
feeding  is  instituted,  although  not  until  some  time 
after  the  beginning  of  the  treatment.  If  the  hair  be 
examined,  it  will  be  found  to  be  dull  and  without  its 
usual  lustre,  sparse  in  places,  prematurely  grey  (in 
cases  where  the  condition  has  persisted  for  some  time), 
with  patches  of  alopecia.  Leopold-Levi  and  H.  de 
Rothschild  draw  attention  to  the  "  eyebrow  sign  " — 
i.e.,  the  scarcity  of  hair  in  the  eyebrows,  with  a  marked 
diminution  of  the  outer  third  of  each  eyebrow.  This 
sign  the  present  writer  believes  to  be  fairly  constant, 
as  he  has  observed  it  in  many  patients  showing  other 
signs  of  thyroid  deficiency. 

Constipation. — The  subjects  of  this  condition  are 
nearly  always  constipated.  As  in  thyroid  excess  the 
reverse  is  the  case  and  the  motions  are  on  the  loose 
side  and  frequent,  so  in  submyxcedema  are  the  bowels 
costive. 

Other  Characteristic  Features. — If  we  can  describe 
a  type  of  "  thyroid  deficients  " — that  is  to  say,  sub* 


THYKOID  DEFICIENCY  97 

jects  of  long-standing  submyxcedema — we  must  lay 
emphasis  on  one  or  two  points.  The  individuals  are 
usually  small,  with  deepset  eyes,  scanty  hair,  dry  skin, 
and  with  the  appearance  of  premature  senility.  They 
require  abundant  sleep,  and  are  particularly  liable  to 
somnolence  after  meals. 

They  are  inclined  to  obesity,  with  the  deposits  of 
fat  which  characterize  this  condition,  thickset,  with 
an  expressionless  face,  possibly  carious  teeth,  and 
gingivitis  or  actual  pyorrhoea. 

Again,  the  subjects  of  thyroid  deficiency  are  very 
prone  to  fatigue,  which  develop es  without  an  undue 
expenditure  of  energy.    In  this  way  they  resemble  the 
neurasthenic,  just  as  in  their  somnolence  after  food 
they  remind  the  observer  of  the  lithaemic  subject.     As 
we  pointed  out  in  a  previous  chapter,  these  patients 
frequently  exhibit   signs   of  premature  senility,   the 
arteries   may   be   thickened,   the   skin   wrinkled,   the 
joints  have  lost  their  suppleness,  as  they  are  wont 
to  do  in  old  age.     We  may  refer  in  passing  to  the 
supposed  relationship  between  the  parathyroid  glands 
and  calcium  metabolism,  as  it  is  assumed  by  many 
observers  that   derangements  of  these  small  glands 
permit  the  retention  in  the  body  of  the  lime  salts, 
which  are   deposited   in  various  parts  of  the   body. 
It  may  be  that  thyroid  deficiency  is  associated  in  many 
of  these  patients  with  a  parathyroid  deficiency,  and 
that  it  is  the  diminution  in  the  latter  secretion  and  not 
in  the  former  which  causes  the  symptoms  of  premature 
senility. 

7 


98    THE  ORGANS  OF  INTERNAL  SECRETION 

It  may  be  helpful  at  this  stage  of  our  study  to  refer 
to  the  work  of  Leopold-Levi  and  H.  de  Rothschild 
on  this  subject.  These  observers  combine  physio- 
logical research  with  clinical  utility,  so  that  the  two 
aspects  of  thyroid  deficiency  are,  so  to  speak,  brought 
into  focus.2  These  authors  refer  to  "  thyroid  in- 
stability " — i.e.,  to  the  liability  to  disturbance  in  the 
normal  working  of  this  gland,  whether  in  the  direc- 
tion of  excess  or  that  of  deficiency.  They  assert  that 
a  simple  excess  (slight  hyperthyroidism)  is  very  liable 
to  be  succeeded  by  a  deficiency,  and  that  the  two 
conditions — hyperthyroidism  and  subthyroidism — are 
frequently  associated  in  the  same  individual.  Thus, 
when  these  two  conditions  are  present  in  the  same 
patient,  the  prominent  features  of  both  might  equally 
well  be  noticed.  Those  pointing  to  excess  of  the 
secretion  of  the  gland,  such  as  palpitation,  nervous- 
ness, exophthalmos,  and  tremors,  are  combined  with 
those  indicating  deficiency,  such  as  constipation, 
chilliness,  sclerodermia,  scanty  hair,  etc.  In  another 
place3  Leopold-Levi  refers  to  the  "  hyperthyroidism 
associated  with  thyroid  deficiency,"  which  he  says 
may  be  classified  as  follows: 

(a)  Paroxysmal  derangements  of  a  hyperthyroidic 
nature,  which  appear  as  simple  reactions  and  may  be 
classed  as  symptoms. 

(b)  Reactions  of  a  more  complex  nature,  the  mani- 
festation of  which  includes  other  symptoms,  and  which 
may  be  classed  as  syndromes. 


THYROID  DEFICIENCY  99 

(c)  Reactions  affecting  the  tigroid  gland  itself 
(endogenous  goitre). 

To  emphasize  the  characteristics  which  we  have 
already  discussed  as  being  present  in  thyroid  deficiency, 
we  will  quote  from  this  same  article  what  this  author 
gives  as  being  the  symptoms  of  a  "  slight  degree  of 
hyperthyroidism,"  as  by  this  means  we  shall  serve  to 
impress  the  two  different  clinical  pictures. 

"  1.  Hypertrichosis,  more  particularly  of  the  eye- 
brow. 

"  2.  Hyperthermia,  flushings,  febricula  of  thyroict 
origin. 

"  3.  Acro-erythrosis,  with  cutaneous  humidity. 

"  4.  Tendency  to  diarrhoea,  the  stools  being  soft 
and  frequent. 

"  5.  Great  physical  restlessness,  with  a  sensation  of 
being  hurried. 

"6.  Insomnia. 

"7.  Emaciation. 

"  8.  Excessive  height. 

"9.  Developmental  precocity. 
'  10.  The    syndrome    which  I  have  named   '  syn- 
drome of  persistent  juvenility.' 

;'  11.  Extreme  nervous  irritability,  with  cardiac  and 
cutaneous  excitability,  etc. 

"12.  Large  brilliant  protruding  eyes,  with  nystagmi- 
form movements. 

"13.  The  reactions  are  generally  excessive,  and  there 
is  exaggeration  of  the  nutritional  exchanges. 

"  14.  Hyperplasia  of  the  entire  thyroid  gland."4 


100  THE  OEGANS  OF  INTERNAL  SECRETION 

It  is,  however,  quite  obvious  that  many  of  these 
symptoms  can  only  be  present  in  those  patients  where 
the  condition  has  been  congenital,  has  commenced 
during  adolescence,  or  has  been  in  existence  for  a  very 
long  time;  for,  to  take  only  one  example,  the  stature 
could  scarcely  be  altered  in  an  adult  patient  who 
develop es  the  condition  after,  let  us  say,  a  severe 
illness.  But,  on  the  other  hand,  there  can  be  little 
doubt  that  many  of  the  symptoms  are  quite  constant, 
and  can  be  observed  in  a  large  proportion  of  cases. 
At  the  present  time  the  writer  of  this  book  has  under 
his  observation  a  lady  who  is  undoubtedly  suffering 
from  deficiency  of  the  thyroid,  but  has  also  the  syn- 
drome which  points  to  excessive  action  of  this  gland. 
Thus,  while  she  has  typical  deposits  of  fat,  ichthyotic 
skin,  characteristic  hair,  somnolence,  and  mental 
turpitude,  she  also  has  slight  tachycardia,  rather 
prominent  eyes,  an  almost  unnoticeable  tremor,  some 
degree  of  nervousness,  and  transitory  restlessness.  In 
fact,  in  this  case  the  picture  changes  from  time  to 
time — sometimes  the  signs  of  excess  in  the  thyroid 
secretion  being  uppermost,  at  other  times  the  signs 
of  deficiency  being  more  noticeable.  There  can  be 
little  doubt  that  in  many  cases  both  conditions  are 
present,  but  not  necessarily  at  the  same  time.  It 
is  quite  possible  that  a  hyperthyroidism  succeeds  a 
transitory  deficiency,  that  while  this  condition  is 
present  the  signs  of  its  presence  are  marked,  but  that 
the  reaction  brings  with  it  exactly  opposite  symptoms- 

The  view  expressed  by  Leopold-Levi — namely,  that 


THYEOID  DEFICIENCY  101 

the  thyroid  can  be  in  an  unstable  condition,  so  that 
both  these  two  opposite  syndromes  can  be  combined 
— is  one  which  is  supported  by  many  observers.  He 
believes,  however,  that  the  two  conditions  are  rarely 
combined  at  the  same  time,  but  that  the  fundamental 
state  is  one  of  "  thyroid  instability."  This,  however, 
may  constitute  a  condition  in  which  the  thyroid 
wobbles,  so  to  speak,  between  outbursts  of  hard  work 
and  spasms  of  idleness.     About  such  a  state  he  says: 

"  Associated  with  thyroid  insufficiency  is  a  large 
number  of  syndromes,  the  characteristic  features  of 
which  are  that  they  are  precipitated  suddenly  in  the 
form  of  thyroid  crises,  and  that  they  yield  to  treatment 
with  thyroid  extract. 

11  Although  associated  with  thyroid  inadequacy, 
these  syndromes  are  the  clinical  expression  of  a  hyper- 
thyroidism which  is,  in  itself,  the  reactionary  mani- 
festation of  the  fundamental  subthyroidic  condition. 

11  They  are — migraine,  ophthalmic  migraine,  asthma, 
nasal  asthma,  attacks  of  chronic  rheumatism  and  gout, 
mucous  enteritis,  urticaria  and  other  skin  affections 
(acne,  eczema),  mental  symptoms."5 

From  this  quotation  the  reader  will  see  that  the 
alteration  in  the  thyroid  is  believed,  by  this  authority 
at  least,  to  present  many  features  which  are  sufficiently 
capable  of  recognition  to  enable  the  diagnostician 
to  arrive  at  an  accurate  judgment.  Before  closing 
this  chapter,  however,  it  may  be  well  to  remember 
that  not  all  these  symptoms  can  be  expected  to  be 
present  in  the  same  patient.     Kather  must  the  physi- 


102    THE  OEGANS  OF  INTEENAL  SECEETION 

cian  be  on  the  lookout  for  any  of  them,  remembering 
that,  so  far  as  the  endocrinous  glands  are  concerned, 
diagnosis  must  be  aided  by  ingenious  detection. 

References. 

1  See  Introduction,  pp.  3-6. 

2  See  "  La  Petite  Insuffisance  Thyroidienne  et  son  Traite- 
nient,"  by  Leopold-Levi  and  H.  de  Rothschild,  published  by 
O.  Doin  et  Fils,  Paris,  1913. 

3  Practitioner,  vol.  xciv.,  No.  2,  p.  211. 

4  Ibid.,  vol.  xciv.,  No.  2,  p.  212. 

5  Ibid.,  p.  213. 


CHAPTER  V 
THYROID  DEFICIENCY  (Continued) 

We  have  now  discussed  the  broad  outlines  of  thyroid 
excess  and  thyroid  deficiency.  But  this  latter  subject 
is  of  such  importance,  if  we  are  to  use  to  the  full  the 
powers  which  a  knowledge  of  organo-therapy  gives  us, 
that  we  propose  to  devote  this  chapter  to  a  more 
detailed  study  of  the  signs  and  symptoms  of  hypo- 
thyroidism. 

Owing  to  the  importance  of  this  subject,  which, 
indeed,  increases  from  day  to  day  as  our  knowledge 
of  the  lesions  which  may  be  attributed  to  disturb- 
ances in  the  hormonic  system  becomes  wider,  it  is 
necessary  for  us  to  discuss  at  some  length  this  aspect 
of  the  endocrinous  glands.  For  thyroid  deficiency 
is  of  the  most  vital  interest  to  all  students  of  medicine, 
if  only  that,  when  recognized  early,  many  aberrations 
from  normal  health  may  be  remedied,  or  even  averted, 
by  the  administration  of  extract  of  the  thyroid 
gland. 

For  this  reason  alone  it  behoves  us  to  make  our- 
selves au  fait  with  the  more  marked  symptoms  of 
this  disorder,  for  many  of  these  will  yield  to  rational 
therapy.     Again,  as  in  every  other  treatment,  there 

103 


104  THE  OEGANS  OF  INTEENAL  SECEETION 

is  a  right  and  a  wrong  way  to  proceed  with  thyroid 
administration,  but,  unfortunately,  this  fact  is  not 
widely  appreciated.  Probably  from  the  erroneous 
impression  as  to  the  dosage  which  is  given  in  text- 
books of  medicine,  and  in  posological  tables,  the 
dose  of  thyroid  extract  is  usually  far  too  high.  In 
any  case  it  is  necessary  to  proceed  cautiously  when 
prescribing  this  drug,  for  the  personal  factor  is  never 
more  important  than  in  thyroid-therapy.  We  shall 
discuss  this  in  more  detail  at  the  end  of  this  chapter. 

In  the  last  chapter  we  reviewed  the  opinions  which 
are  held  as  to  the  symptomatology  of  thyroid  defici- 
ency, and  quoted  the  views  of  Leopold-Levi  and  H. 
de  Eothschild.  We  referred  to  "  thyroid  instability," 
to  the  syndromes  which  these  authors  believe  to  be 
characteristic  of  thyroid  excess  and  thyroid  deficiency, 
and  to  their  belief  that  the  two  conditions  may  be 
present  successively  or  even  concurrently  in  the  same 
patient.  The  opinions  expressed  by  these  observers 
are  important,  for  they  have  made  a  careful  study 
of  the  thyroid  gland  and  its  disorders,  and  their 
conclusions  are  of  the  greatest  help  to  anyone  wishing 
to  familiarize  himself  with  thyroid  dosage. 

Harrower  quotes  in  his  book  on  "  Practical  Hormone- 
Therapy  "  from  Leopold-Levi  and  H.  de  Eothschild's 
book  on  "La  Petite  Insurnsance  Thyroidienne." 1 
These  authors  say:  "  Considerable  importance  attaches 
to  minor  thyroid  insufficiency,  for,  unlike  myxoedema, 
it  is  very  frequent.  It  should  be  also  especially 
interesting  to   the   physician   because   of  its   usually 


THYROID  DEFICIENCY  105 

rapid  response  to  treatment.  Clinical  experience  is 
the  basis  of  these  deductions,  just  as  it  was  the  original 
basis  of  the  present  knowledge  of  the  stigmata  of 
hypothyroidism." 

Now,  let  us  spend  some  time  in  studying  those 
points  which  are  generally  considered  to  be  typical 
of  thyroidic  insufficiency.  We  have  already  studied 
the  main  symptoms,  and  the  manner  in  which  normal 
physiological  processes  are  altered  in  the  absence  or 
perversion  of  thyroid  secretion.  Our  object  now  is  to 
study  the  type  which  makes  one  look  for  symptoms 
rather  than  the  symptoms  themselves. 

The  following  may  be  said  to  be  points  in  bodily 
construction  which  suggest  faulty  thyroid  secretion. 
As  we  have  already  said,  these  patients  are  small. 
Their  stature  is  frequently  diminutive,  while  the 
development  of  their  soft  structures  is  excessive  in 
proportion.  There  is  also  present,  according  to 
Hertoghe,  a  relaxed  condition  of  the  articular  liga- 
ments, which  permits  of  over-extension  of  the  joints. 
Thus,  we  shall  look  for  what  is  known  in  popular 
language  as  "  double- jointed  "  people.  The  patient 
to  whom  we  referred  in  the  last  chapter  (in  whom 
symptoms  suggestive  both  of  excess  and  insufficiency 
were  present)  showed  this  symptom  remarkably  well. 
She  was  able  to  bend  her  fingers  back  until  the  nails 
almost  touched  the  back  of  the  hand.  In  this  con- 
nection, Hertoghe  refers  to  a  man  who  had  been  under 
his  care  for  a  number  of  years  suffering  from  thyroid 
insufficiency,  in  whom  there  was  spontaneous  painless 


106  THE  OBGANS  OF  1NTEKNAL  SECRETION 

dislocation  of  the  patella.  So  impressed  is  Hertoghe 
with  the  changes  in  this  respect  that  he  says  "it  is 
possible,  with  very  little  practice,  to  judge  of  the  degree 
of  thyroid  inadequacy  merely  by  squeezing  the  patient's 
hand."2  He  says  that  these  hands  give  the  impression, 
when  squeezed,  of  a  "  glove  filled  with  clay." 

The  present  writer  is  certainly  of  the  opinion  that 
the  relaxation  of  the  ligamentous  structures  in  sub- 
myxcedema  is  something  more  than  an  artificial 
symptom.  He  has  noticed  it  in  a  number  of  patients 
affected  with  this  disease,  in  which  the  diagnosis  was 
confirmed  by  treatment. 

Nevertheless,  it  must  be  remembered  that,  in 
describing  a  type  of  submyxcedema,  we  are  only 
dealing  with  long-standing  cases  or  with  the  individuals 
in  whom  there  has  been  a  deficiency  since  infancy.  It 
is  obvious  that,  where  the  disorder  commences  in 
adult  life — for  instance,  after  an  infection — we  shall  not 
expect  to  see  the  signs  of  a  type  such  as  we  have  just 
described. 

In  children  certain  signs  of  thyroid  deficiency  have  to 
be  added  to  those  for  which  one  must  look  in  an  adult. 
Thus,  while  growth  is  impaired  and  stature  infantile, 
we  have  learned  to  expect  a  protuberant  abdomen, 
a  lumbar  lordosis,  due  to  relaxation  of  the  spinal  liga- 
ments, sometimes  abnormalities  of  development,  such 
as  umbilical  hernia,  undescended  testes,  and  so  on. 

Again,  as  such  children  grow  up,  they  continue  to 
show  these  and  similar  signs,  which  are  mere  noticeable 
owing   to   adolescence.      The   sexual   development   is 


THYROID  DEFICIENCY  107 

delayed,  immature  sexual  organs  only  being  present 
in  many  cases,  the  stature  remains  stunted,  and  there 
is  faulty  mental  development.  The  exhibition  of 
thyroid  extract  serves  to  increase  stature,  remedy 
faulty  development  in  other  directions,  and  even  to 
abolish  symptoms  such  as  umbilical  hernia.  If  omitted 
too  soon,  or  if  given  in  insufficient  doses,  the  improve- 
ment is  apt  to  cease  and  the  growth  to  stop. 

This,  then,  is  what  to  expect  in  subthyroidic  children ; 
if  exaggerated,  we  meet  cretinism.  Such  children 
are  deficient  in  hair,  and  may  even  show  more  or  less 
generalized  alopecia.  This,  when  combined  with  the 
infantile  expression  of  the  face,  should  at  once  make 
one  suspect  thyroid  deficiency.  The  child  may  be 
small  for  his  age;  he  may  present  one  or  more  of  the 
stigmata  referred  to  above;  and,  finally,  the  diagnosis 
is  clinched  by  the  exhibition  of  thyroid  extract  and 
the  resulting  improvement. 

So  much,  then,  for  thyroid  deficiency  in  a  child. 
What  produces  this  is  a  more  difficult  question. 
There  can  be  little  doubt  that  in  many  cases  the 
tendency  is  an  inherited  one.  These  children  often 
come  from  stock  which  can  be  shown,  on  careful 
examination  and  questioning,  to  be  subthyroidic. 
Hertoghe  quotes  a  case  of  infantilism  of  the  Lorain 
type,  the  mother  of  the  child  being  a  myxcedematous 
subject  of  a  benign  type. 

Like  many  other  diseases,  prenatal  conditions  must 
be  blamed  for  many  of  these  cases,  and  it  will  have 
already  been  noticed  how  some  of  the  defects,  due 


108  THE  ORGANS  OF  INTERNAL  SECRETION 

to  imperfect  development,  are  more  or  less  directly 
traceable  to  the  thyroid  gland,  as  they  are  remedied 
after  birth  by  the  administration  of  the  extract  of  this 
gland.  In  support  of  this,  witness  the  umbilical  hernia 
in  one  of  Hertoghe's  cases,  and  note  how  it  cleared  up 
when  the  child  had  been  taking  thyroid  for  some  time. 
Again,  it  will  be  remembered  that  such  stigmata  as 
imperfect  development  of  the  bones  are  among  the 
signs  of  inherited  syphilis;  while  it  has  been  stated 
that  the  administration  of  thyroid  extract  is  as  effica- 
cious as  iodide  of  potassium  in  healing  tertiary  syphilitic 
lesions.3 

Two  other  functions  of  the  thyroid  are  pertinent  to 
our  study.  First,  we  have  to  remember  the  theory 
which  deals  with  the  "  antitoxic  "  power  of  this  gland, 
and  to  bear  in  mind  that,  if  this  is  true,  the  subjects 
of  any  kind  of  thyroid  deficiency  must  needs  be  more 
open  to  bodily  infection,  either  from  so-called  auto- 
genetic  or  heterogenetic  sources.  Second,  as  pointed 
out  by  Hertoghe,  the  life  of  each  cell  of  the  body, 
considered  as  an  individual,  is  relatively  a  short  one. 
It  serves  its  purpose,  degenerates,  and  is  excreted  from 
the  body  by  one  of  the  normal  channels.  For  this 
to  be  performed,  however,  in  a  normal  manner,  the 
presence  of  thyroid  secretion  is  necessary;  for  in  its 
absence  such  cell  elimination  does  not  follow  its  usual 
course.  Hence  the  vast  increase  in  the  subcutaneous 
tissue  which  is  present  in  myxoedema,  and  to  a  less 
degree  in  submyxoedema.  As  is  so  well  known,  this 
gives  rise  to  oedema,  or,  to  be  accurate,  to  increased 


THYEOID  DEFICIENCY  109 

subcutaneous  tissue,  which  pits  on  pressure.  Extract 
of  thyroid  gland  diminishes  this  abnormal  subcutaneous 
tissue,  and  in  so  doing  lessens  the  bodily  weight. 
The  excretion  of  nitrogen  is  increased  by  this  extract, 
so  that  the  elimination  of  broken-down  cells  is  restored 
to  normal — another  reason  for  the  reduction  in  weight 
under  thyroid  feeding. 

As  we  have  said  already,  the  submyxcedematous 
patient  is  habitually  constipated,  and  this  may  have 
an  effect  to  which  we  drew  attention  in  a  former 
chapter.  These  patients  show  many  of  the  signs 
upon  which  Lane  lays  emphasis  as  indicative  of 
intestinal  stasis;  in  fact,  one  of  these  signs  is  atrophy 
of  the  thyroid.  The  question  to  be  answered  is  this: 
Is  the  thyroid  primarily  responsible  for  the  inertia 
of  the  intestine,  or  does  this  latter  factor  produce 
atrophy  of  the  thyroid  ? 

I  have  seen  cases  which  would  argue  that  Lane's 
view  is  the  correct  one;  on  the  other  hand,  many 
patients  impress  one  more  in  favour  of  the  theory 
that  the  thyroid  atrophy  is  responsible  for  the  signs 
to  which  both  the  supporters  of  the  alimentary  theory 
and  those  who  uphold  the  "  primary  thyroid  defici- 
ency "  theory  lay  claim.  A  short  time  ago  I  saw  a 
lady  who  was  complaining  of  vague  pains  in  the 
extremities,  dry  and  itching  skin,  languor  and  lack  of 
mental  alertness,  and  constipation.  On  examination 
I  found  a  swelling  of  the  thyroid  gland,  a  slow  pulse 
and  an  ichthyotic  condition  of  the  epidermis.  Further- 
more, there  was  a  good  deal  of  evidence  of  intestinal 


110   THE  OKGANS  OF  INTERNAL  SECRETION 

stasis,  such  as  meteorism,  offensive  flatus,  insufficient 
motions  even  after  a  purge,  and  digestive  disturb- 
ances. To  many  of  those  students  who  have  read  Sir 
Arbuthnot  Lane's  work  upon  the  subject  of  intestinal 
stasis,  the  signs  indicative  of  intestinal  stasis  were 
all  (I  refer  to  the  main  signs,  and  not  to  the  smaller 
indications)  present.  At  the  same  time  the  student 
of  opo- therapy  would  find  most  of  the  signs  which  he 
has  learnt  to  regard  as  pathognomonic  of  thyroid 
deficiency  present  in  this  case.  The  stature  was  small, 
the  hair  atrophic,  the  skin  dry,  the  pulse  slow,  the 
bowels  costive.  I  need  hardly  enumerate  the  other 
well-known  signs. 

Any  observer  dealing  with  functional  disturbances 
is,  however,  bound  to  be  struck  with  the  frequency  of 
intestinal  disturbances  in  these  patients.  It  may  be 
said  that  constipation  is  an  almost  universal  com- 
plaint, and  that  too  much  stress  has  of  late  been  laid 
upon  it  as  an  etiological  factor,  and  that  its  presence 
in  the  subthyroidic  is  secondary  to  the  endocrine 
disorganization.  This  argument  is,  at  least,  open  to 
question.  If  the  thyroid  functions  as  a  filter,  it  is 
equally  likely  that,  where  toxins  are,  or  have  been, 
at  work,  we  shall  find  a  drying-up  of  the  thyroid 
secretion. 

There  we  must  leave  the  discussion  of  the  primary 
cause,  as  there  is  insufficient  evidence  to  warrant  us 
in  dogmatizing  further  on  the  why  and  the  wherefore 
of  thyroid  atrophy. 


THYEOID  DEFICIENCY  111 

In  reading  the  mass  of  literature  which  has  accumu- 
lated of  recent  years  on  this  subject,  the  reader  is 
struck  with  the  many  different  signs  which  are  believed 
by  the  majority  of  observers  of  organo-therapy  to  be 
caused  by  thyroid  insufficiency.  Even  if  at  first  glance 
one  is  inclined  to  believe  that  the  clinical  picture  of 
submyxcedema  has  been  exaggerated,  yet,  if  one  realizes 
the  signs  which  a  severe  degree  of  thyroid  deficiency 
produces,  one  can  scarcely  doubt  that  a  minor  degree 
might  very  well  alter  the  individual,  although  in  a 
slighter  degree;  indeed,  in  the  very  mild  cases  to  so 
small  a  degree  as  to  make  the  change  all  but  im- 
perceptible. 

The  main  object  of  this  chapter  is  to  bring  the 
practical  points  in  connection  with  hypothyroidism 
before  the  notice  of  those  whose  time  does  not  permit 
of  the  perusal  of  the  latest  physiological  and  clinical 
research,  so  that  a  greater  percentage  of  patients 
who  might  be  helped  by  organo-therapy  (and  who 
will  in  all  probability  be  helped  by  no  other  means) 
shall  benefit  by  our  knowledge,  which  has  increased 
every  year  since  Murray's  original  discovery.  The 
study  of  the  changes  wrought  in  the  various  parts  of 
the  body  by  an  absence  or  diminution  in  the  secretion 
of  the  thyroid  are  so  numerous  that  it  will  be  best  to 
deal  with  them  separately,  classing  them  under  the 
different  bodily  systems.  We  will  therefore  study 
them  in  this  way. 


112   THE  OEGANS  OF  INTEKNAL  SECRETION 

The  Influence  of  the  Thyroid  Secretion  upon 
the  Ceil. 

Throughout  life  the  living  cell  requires  certain 
hormones  if  it  is  to  follow  the  normal  cycle  of  life. 
Thus,  if  starved  of  thyroid  its  growth  is  impaired; 
administer  to  the  individual  organism  the  extract  of 
this  gland,  and  growth  is  resumed.  This  is  shown 
by  the  behaviour  of  cretins  to  thyroid  feeding;  they 
improve  in  every  way  under  such  treatment,  but 
relapse  if  it  is  stopped  or  diminished.  We  have  already 
pointed  out  that  broken-down  cells  which  should  be 
eliminated  are  retained  and  stored  (in  a  form  that 
originally  was  thought  to  be  mucinous)  if  the  thyroid 
secretion  is  diminished.  Thus,  the  cycle  of  growth 
and  decay  are  both  interfered  with,  if  the  endocrinous 
system  is  disturbed.  In  association  with  this,  we 
must  explain  one  or  two  important  facts.  The  subject 
of  thyroid  deficiency  is  never  "fit";  he  is  generally 
tired,  he  finds  work  a  burden,  and,  whether  his  employ- 
ment is  physical  or  mental,  he  requires  a  "push" 
before  he  can  make  himself  take  up  his  tools.  Again, 
his  mental  apparatus  fails  him,  his  memory  is  un- 
reliable, he  cannot  recall  either  recent  or  past  events; 
his  attention  wanders;  his  concentration  is  never  at 
its  brightest  when  he  wishes  to  solve  a  problem;  and, 
in  a  word,  he  is  sluggish  mentally  as  he  is  languid 
physically.     He  is  neurasthenoid. 

The  muscular  system,  in  association  with  the  sub- 
cutaneous, ligamentous,  and  fascial  systems,  undergoes 


THYEOID  DEFICIENCY  113 

infiltration;  while  the  nerve  cell  "  suffers  derangement 
of  nutrition."  It  becomes  "  infiltrated,  and  it  also 
undergoes  compression,  as  the  result  of  the  infiltration 
of  the  connective  tissue  surrounding  it.  Hence,  the 
transmission  of  motor  and  sensory  impulses,  both 
voluntary  and  involuntary,  though  delayed,  is  in  no 
sense  abolished.  The  reflexes  are  tardy,  but  they 
are  present."4 

Therefore  the  cells  of  the  nervous  system  are  em- 
barrassed in  a  double  manner — from  within  and  with- 
out. The  infiltration  of  fascia,  of  'muscle,  and  of 
sheath,  must  of  necessity  exaggerate  the  difficulty 
of  exertion.  This  would  apply  both  to  physical  and 
mental  exertion. 


Symptoms  Referable  to  Nervous  Tissue. 

Apart  from  the  mental  sluggishness,  which  we  have 
already  described,  these  patients  suffer  from  a  variety 
of  ailments  more  or  less  directly  referable  to  the  nervous 
system.  Thus,  they  are  very  liable  to  headache, 
which  is  usually  frontal,  but  occasionally  occipital. 
The  two  forms,  however,  are  rarely  merged.  The 
headache  of  thyroid  insufficiency  is,  in  nearly  every 
case,  worse  in  the  morning,  improving  as  the  day 
wears  on. 

Giddiness  is  another  constant  symptom,  with  which 
is  associated,  in  some  cases,  a  "  swimming  "  sensation. 
Tinnitus  aurium,  either  in  the  form  of  buzzing,  roaring, 
whistling,  or  shrieking  noises,  is  common,  while  these 

8 


114   THE  OEGANS  OF  INTERNAL  SECRETION 

patients  sometimes  experience  even  more  serious 
sensory  disturbances,  such  as  hearing  voices,  the 
ringing  of  bells,  etc.5  In  practice,  many  such  cases 
have  been  benefited  by  the  administration  of  thyroid 
extract.  So  far  as  I  am  aware,  there  is  no  evidence 
that  true  vertigo  is  seen,  although  I  have  prescribed 
this  extract  for  one  or  two  patients  in  whom  the 
giddiness  and  dizziness  were  very  similar  to  true 
vertigo. 

We  have  already  referred  to  the  functional  nervous 
changes  which  are  seen  in  thyroid  deficiency,  of  which 
somnolence  is,  perhaps,  one  of  the  most  marked. 
These  patients  seem  to  be  able  to  sleep  very  soundly 
at  night,  after  every  meal,  and  at  any  other  time  when 
the  opportunity  offers.  Most  subthyroidics  complain 
of  their  marked  tendency  to  slumber  at  all  times, 
and  the  more  intelligent  find  that  it  is  sufficiently 
marked  to  be  abnormal.  In  spite  of  this,  these 
patients  do  not  wake  up  refreshed,  and  they  feel  worse 
in  the  morning  than  they  do  at  night.  Hertoghe 
suggests  that  "  in  all  probability  the  thyroid  neutralizes 
the  toxins  generated  during  the  hours  of  activity 
during  the  night — that  is,  under  normal  physiological 
conditions — but  that  this  does  not  happen  in  the 
subject  of  thyroid  deficiency."6 

We  have  already  dealt  with  the  changes  in  the 
mental  apparatus  which  must  be  looked  for  in  sub- 
myxcedema;  to  the  confusion  of  mind  and  the  lack  of 
mental  initiative  we  must  attribute  the  slowness  of 
thought,  as  well  as  the  lack  of  confidence,  which  these 


THYROID  DEFICIENCY  115 

patients  show.  To  these  facts  also  we  must  attribute 
the  undue  exertion  which  any  work  demands  from 
these  patients. 

The  Subcutaneous  and  Muscular  Tissue. 

The  thickening  seen  in  thyroid  inadequacy  is 
characteristic.  It  involves  all  tissue,  according  to 
most  observers,  but  in  certain  areas  it  is  laid  down  more 
or  less  in  "  heaps."  Thus,  the  nape  of  the  neck  down 
to  the  last  cervical  vertebra  shows  a  thickening,  while 
in  the  last-named  area  is  almost  always  seen  a  mass 
of  fat  which  resembles  a  lipoma.  Particularly  is  this 
so  in  adult  patients,  more  especially  in  the  female 
sex.  The  head  is  held  somewhat  forward  ("  cassowary 
neck  "),  so  that  the  cervical  deposit  appears  more 
prominent  than  is  really  the  case.  The  shoulders  of 
such  patients  are  broad,  while  the  clavicular  regions 
contain  pads  of  fat. 

Such  deposits  of  fat  as  these  are  more  or  less  de- 
pendent on  sluggish  circulation,  and  therefore  regions 
such  as  the  abdominal  wall  are  apt  to  suffer.  The 
flanks  and  back  are,  in  adult  patients,  enlarged  by 
rolls  of  fat,  while  the  bones  of  the  extremities  are 
sunken  in  an  envelope  of  adipose  tissue.  This  deposit 
is  not  solely  fatty,  nevertheless  it  adds  to  the  body- 
weight  considerably  and  hampers  bodily  activity. 
The  entire  subcutaneous  integument  appears  to  be 
thickened,  and  this  thickening  can  be  made  to  pit  on 
pressure,  although  the  pitting  disappears  as  soon  as 
the  pressure  is  relaxed. 


116  THE  OEGANS  OF  INTEENAL  SECEETION 

As  regards  the  changes  in  the  muscular  system,  we 
can  by  reason  of  these  changes  explain  several  symp- 
toms from  which  these  patients  suffer.  The  muscles 
are  burdened  with  fat  and  mucinous  infiltration, 
so  that  their  size  is  increased  and  their  drainage 
insufficient.  Muscular  movement  is  hampered,  so  that 
the  metabolic  exchanges  are  even  more  restricted. 
Hence  the  dislike  of  active  exercise  which  these  patients 
invariably  show.  Again,  the  increase  in  the  volume 
of  the  musculature  leads  to  discomfort,  if  not  actual 
pain,  which  latter  may  be  vastly  relieved  by  the 
exhibition  of  thyroid  extract. 

It  is  well  known  that  children  who  are  the  subjects 
of  thyroid  inadequacy  are  very  prone  to  the  develop- 
ment of  adenoids,  and  that  this  is  one  of  the  charac- 
teristic stigmata  of  this  condition.  Again,  in  such 
subjects  the  enlargement  of  lymphatic  glands  is 
common,  and  some  thickening  of  these  structures  is 
frequently  observed. 

Sweating  is  practically  unknown  in  submyxcedema, 
per  se,  and  in  consequence  there  is  some  increase  in  the 
secretion  of  the  kidneys,  with  a  tendency  to  nocturnal 
enuresis.  The  solids  of  the  urine  are,  of  course, 
diminished,  but  increase  enormously  when  the  patient 
is  taking  thyroid.  The  nocturnal  enuresis  from  which 
these  patients  suffer  is  in  part,  at  any  rate,  due  to  the 
extreme  heaviness  with  which  they  sleep;  and  for 
some  years  now  thyroid  extract  has  been  prescribed 
empirically  for  this  condition,  although  the  under- 
lying causation  was  not  understood  in  the  same  way 


THYROID  DEFICIENCY  117 

as  it  now  is.  This  medication  has  given  very  good 
results  in  many  cases,  but  it  is  almost  infallible  where 
the  underlying  condition  is  one  of  thyroid  inadequacy. 
The  absence  of  adequate  secretion  from  the  skin — 
and  these  subjects  rarely  sweat — results  in  a  stagnant 
condition  of  the  liver;  and,  according  to  Hertoghe, 
this  results  in  itching  of  the  skin,  the  icterus  of  myx- 
cedema.  It  may  also  assist  in  the  intense  drowsiness, 
if  not  also  in  the  slow  pulse;  but  even  if  so,  it  would 
only  be  a  contributory  factor.  It  is,  however,  quite 
conceivable  that  the  constipation  is  partly  due  to 
diminution  of  the  normal  biliary  secretion  in  the 
intestine,  the  natural  laxative. 

The  Osseous  and  Cartilaginous  Systems. 

The  delayed  growth  resulting  from  a  deficient 
thyroid  secretion  is  too  well  known  to  demand  lengthy 
description.  So  long  as  the  epiphyses  are  not  ossified, 
there  remains  the  possibility  of  renewal  of  growth 
under  thyroid  feeding.  This  can  be  ascertained  by 
the  Rontgen  rays. 

Again,  myxcedema  produces  its  characteristic  in- 
filtration in  the  joints  and  their  ligamentous  structures. 
This  causes  crackling  in  the  joints,  and  gives  the 
impression  of  a  rheumatoid  condition.  When  this 
sign  is  present,  therefore,  a  careful  search  should  be 
made  for  other  symptoms  pointing  to  thyroid  defici- 
ency. It  has  been  said  that  delayed  union  after 
fracture   is   very   common   in   subthyroidic   subjects, 


118   THE  OEGANS  OF  INTERNAL  SECRETION 

and  that  the  bone  unites  on  the  exhibition  of  thyroid 
extract. 

Epidermal  Symptoms. 

The  dry,  rough,  and  ichthyotic  skin  which  character, 
izes  these  subjects  has  already  been  described.  From 
their  point  of  view,  this  is  probably  one  of  the  most 
troublesome  features,  as  the  inconvenience  of  a 
generalized  itching  cannot  well  be  exaggerated. 
There  is  little  to  be  seen  on  examining  the  skin  of 
these  patients  beyond  what  we  have  already  described. 
The  hair  suffers  in  common  with  other  epidermal 
appendages.  The  nails  are  brittle  and  grooved,  or 
they  may  be  actually  cracked.  As  we  have  already 
said,  the  "eyebrow"  sign,  first  described  by  Leopold- 
Levi  and  H.  de  Rothschild,  is  of  considerable  diagnostic 
significance.  There  is  a  sparseness  of  the  outer  third 
of  each  eyebrow,  with  a  scarceness  and  partial  falling 
out  of  the  whole  eyebrow.  This  feature  can  be  seen 
in  many  subthyroidics,  and  should  always  be  remem- 
bered when  looking  for  confirmatory  evidence  of  a 
suspected  inadequacy  of  this  secretion. 

Pigmentation  of  the  skin,  perhaps  more  commonly 
seen  on  the  forehead,  and  raising  of  the  eyebrows, 
are  both  characteristic;  while  the  lips  are  usually 
thickened,  and  the  mouth  tends  to  open.  The  changes 
in  the  facial  characteristics  give  an  unusually  stupid 
appearance  to  the  patient,  but  this  changes  under 
thyroid  feeding.  The  more  marked  cases  of  thyroid 
insufficiency   develope   countenances   which   resemble 


THYEOID  DEFICIENCY  119 

nothing  so  much  as  a  porker;  and  the  change  which 
is  brought  about  in  the  expression  as  treatment 
proceeds  is  most  gratifying  to  the  patient  himself,  as 
well  as  his  relatives  and  friends. 

In  adult  subthyroidics  the  hair  is  prematurely  grey, 
and  this  change  in  colour  is  usually  more  marked 
over  the  temples.  In  the  case  which  I  published  in 
the  British  Medical  Journal  of  June  20,  1914,  this 
feature  was  well  shown,  although  the  patient  was  a 
young  man  about  twenty-eight  years  of  age.  If  the 
hair  is  a  normal  colour,  it  is  frequently  without  gloss, 
and  is  brittle  and  "  lifeless."  Patches  of  alopecia 
are  common,  and  the  scalp  as  a  whole  is  dry  and 
scaly. 

It  must  be  remembered  that  pigmentation  of  the 
skin  is  seen  in  thyroid  excess  as  well  as  in  thyroid 
deficiency,  and  that  it  is  a  characteristic  feature 
of  Addison's  disease.*  As  a  diagnostic  symptom, 
therefore,  it  is  not  of  great  value. 

Sexual  Symptoms. 

During  childhood  the  diminution  or  absence  of  the 
thyroid  secretion  prevents  the  normal  development  of 
the  genital  organs  at  puberty.  In  fact,  such  patients 
grow  up  to  adult  years  without  any  change  from  the 

*  The  bronzing  characteristic  of  an  adrenal  deficiency  disease — 
e.g.,  Addison's  disease — has  its  analogue  in  the  brown  pigmenta- 
tion seen  in  submyxcedema.  These  stains  disappear,  in  some 
patients,  under  thyroid  medication.  An  instance  of  this  is 
recorded  in  Chapter  XIII.,  p.  298,; 


120   THE  OEGANS  OF  INTERNAL  SECRETION 

infantile  character  of  these  organs.  Indeed,  in  some 
cases  more  serious  defects  are  seen;  for  cryptorchidism, 
either  complete  or  unilateral,  may  be  present.*  In 
cretinism,  of  course,  there  is  no  development  of  any 
sexual  characteristics,  and  the  child  remains  in  this 
respect  unchanged. 

Graves'  disease  produces  a  diminution  of  the  periods, 
either  with  scanty  menstruation  or  amenorrhcea.  The 
reverse  is  true  in  submyxcedema,  for  here  there  is  a 
tendency  towards  menorrhagia,  although  the  periods 
do  not  as  a  rule  develope  until  the  patient  is  well  past 
the  usual  time.  The  uterus  remains  undeveloped, 
or  at  all  events  partially  so,  while  the  ovaries  are 
likewise  immature.  There  is  sometimes  a  marked 
retroversion. 

The  changes  brought  about  in  thyroid  inadequacy 
by  pregnancy  are  for  the  best;  while  the  patient  is 
pregnant  the  thyroid  secretion  is  increased.  But, 
unfortunately,  this  improvement  is  not  permanent, 
and  she  retrogresses,  so  far  as  this  is  concerned,  after 
delivery.  Immediately  after  delivery  there  is  too 
much  secretion,  but  later  this  ceases,  and  the  former 
condition  of  subthyroidism  is  reverted  to.  According 
to  Hertoghe,  some  of  the  increased  thyroid  secretion 
is  directed  towards  establishing  uterine  involution, 
while  another  function  of  this  important  secretion  at 
such  times  is  to  establish  lactation. 

*  An  interesting  case  in  which  delayed  descent  of  the  testes 
was  treated  with  success  by  organo therapy  is  recorded  on  p.  305. 


THYBOID  DEFICIENCY  121 

Gastro-Intestinal  Symptoms. 

In  considering  the  gastro -intestinal  symptoms  of 
thyroid  inadequacy,  we  must  refer  again  to  the  syn- 
drome, which  Lane  attributes  to  intestinal  stasis, 
but  which  observers  in  organo- therapy  claim  to  be 
caused  by  the  thyroid.  "  The  symptoms  are  hypo- 
thermia, uncontrollable  headache,  rheumatoid  pain 
and  neuralgia,  mental  depression,  dyspnoea,  asthmatic 
attacks,  premature  greyness  and  baldness,  dental 
caries,  cholelithiasis,  and  brownish  pigmentation  of 
the  skin."  Thus  Hertoghe  refers  to  this  syndrome, 
and  he  attributes  the  gastro-intestinal  symptoms  of 
thyroid  insufficiency  to  infiltration  of  the  muscular 
tissue  of  the  intestines,  causing  partial  paresis.  This 
in  turn  leads  to  ptosis,  or  partial  ptosis,  and  then  we 
have  kink  formation  and  the  other  features  so  carefully 
described  in  Lane's  book.7 

We  must  emphasize,  in  passing,  what  we  believe  to 
be  a  very  important  aspect  of  this  condition — namely, 
weakening  of  the  abdominal  wall,  which  fails  to  give 
that  support  upon  which  the  intestines  have  come  to 
rely.  This  may  be  due  to  degenerative  processes  of 
an  infiltrative  nature,  or  to  some  other  cause,  but  in 
any  case  the  weakening  helps  the  intestinal  derange- 
ments. This  in  turn  affects  the  digestive  functions; 
appetite,  which  is  notoriously  capricious  in  sub- 
thyroidics,  is  poor;  digestion  is  imperfect,  and  assimila- 
tion lessened.  These  patients  are  always  weak  and 
incapable  of  sustained  effort.     This  is  probably  due 


122   THE  OEGANS  OF  INTEKNAL  SECEETION 

in  part  to  the  causes  already  enumerated,  and  partly 
to  deficient  assimilation  of  food. 

The  association  between  subthyroidic  conditions 
and  septic  affections  of  the  alimentary  tract,  such  as 
appendicitis,  has  often  been  commented  upon,  while 
it  is  said  that  the  relation  between  tonsillitis  and 
appendicitis  is  a  close  one. 

Eectal  haemorrhage  is  said  to  be  common  in  this 
condition,  and,  according  to  Hertoghe,  it  is  due  to 
premature  thickening  of  the  rectal  veins  and  to  the 
deficient  coagulation  of  the  blood.  Just  as  the  monthly 
period  is  apt  to  be  excessive,  so  is  the  hseraorrhage 
due  to  piles,  etc.,  liable  to  be  copious. 

Treatment. 

We  have  now  outlined  the  main  changes  which  may 
be  observed  in  subthyroidic  patients,  and  the  chief 
signs  by  which  the  condition  may  be  recognized.  All 
that  now  remains  to  be  done  is  to  summarize  our 
conclusions  in  a  few  words,  and  to  outline  the  treat- 
ment. 

Whether  the  condition  is  in  evidence  during  child- 
hood or  not  until  after  adolescence,  the  main  features 
are  characteristic.  The  change  in  the  bodily  temper- 
ature is  constant  (a  subnormal  temperature  is  nearly 
always  present),  likewise  the  pulse  is  slow.  These  two 
points  should  always  be  investigated.  Having  deter- 
mined the  condition  of  the  temperature  and  pulse, 
the  skin  and  hair  should  be  examined,  and  a  careful 


THYEOID  DEFICIENCY  123 

investigation  undertaken  to  determine  the  bodily 
weight  and  the  characteristics  of  the  subcutaneous 
tissue.  The  deposits  of  fat,  if  present,  are  usually 
localized.  On  the  other  hand,  the  patient  may  not 
necessarily  be  obese  if  the  degree  of  thyroid  deficiency 
is  slight.  In  such  cases  careful  observation  must  be 
made  to  ascertain  whether  other  signs  are  in  evidence, 
and,  if  so,  whether  the  sum  of  the  signs  and  symp- 
toms points  to  submyxcedema.  The  condition  of  the 
digestion  and  the  bowels,  the  nature  of  the  monthly 
period  in  women,  the  presence  or  absence  of  sensations 
of  chilliness,  of  flushings,  and  of  pains  in  the  limbs, 
should  be  ascertained. 

Having  reached  this  stage  in  the  investigation,  the 
further  points  which  suggest  themselves  for  examina- 
tion deal  with  the  minor  changes  which  are  character- 
istic of  this  disease.  Any  change  in  the  voice,  in  the 
expression,  or  in  the  mental  outlook,  which  either  the 
patient  or  her  relatives  have  noticed,  is  of  importance. 
The  functional  efficiency  of  the  patient  should  be 
studied,  bodily  weakness  and  fatigability  examined, 
and  the  patient  questioned  as  to  the  length  of  time 
these  changes  have  been  noticed. 

All  the  minor  points  are  important,  as  the  question 
of  treatment  depends  upon  these.  We  cannot  empha- 
size too  strongly  the  fact  that,  so  far  as  submyxcedema 
is  concerned,  the  initial  dose  should  be  small.  Even 
if  this  should  be  so  small  as  to  appear  to  the  inexperi- 
enced prescriber  to  be  useless,  it  is  infinitely  preferable 
to  order  a  small  dose,  and  to  continue  this  over  a 


124  THE  OKGANS  OF  INTEKNAL  SECBETION 

lengthy  period,  than  to  commence  with  a  big  dose 
and  have  to  suspend  treatment  on  account  of  un- 
toward reaction. 

In  severe  cases — i.e.,  where  definite  myxoedema  is 
present — the  initial  dose  may  be  larger;  but  such  cases 
do  not  nowadays  form  the  majority  of  patients,  as 
they  are  usually  far  outnumbered  by  the  patients  who 
show  the  signs  of  minor  degrees  of  hypothyroidism # 
Where  myxoedema  is  present,  the  patient  may  be 
given  one,  two,  or  three  5-grain  tablets  of  thyroid 
substance  in  a  day;  or,  if  it  is  preferred,  a  liquid 
preparation  may  be  prescribed,  such  as  Elixir  Colloid 
(Squire)  or  the  Liquor  Thyroidei  (B.P.).  The  dose  of 
Elixir  Colloid  is  from  1  to  2  drachms,  but  even  smaller 
quantities  may  be  given  (1  drachm  represents  1£ 
grains  of  the  dry  extract) ;  while  the  Liquor  Thyroidei 
is  given  in  doses  ranging  from  5  to  15  drops.  Needless 
to  say,  these  doses  must  be  given  entirely  according 
to  the  individual  case,  as  under  no  circumstances 
should  thyroid  medication  be  undertaken  by  rule  of 
thumb.  Each  case  must  be  treated  on  its  individual 
characteristics,  the  length  of  time  during  which  the 
disease  has  been  manifest,  the  degree  of  thyroid 
deficiency,  and  the  alterations  in  the  patient  which 
this  has  produced. 

Kendall,  of  the  Mayo  Foundation,  Eochester, 
Minn.,  has  isolated  a  crystalline  substance  from 
the  thyroid  gland  containing  60  per  cent,  of  iodine. 
This  he  designates  alpha-iodine  compound.  The 
results    following    the   treatment  of    myxoedema   by 


THYEOID  DEFICIENCY  125 

this  preparation  are  reported  to  be  extraordinarily 
good. 

When  we  come  to  the  treatment  of  the  lesser  degrees 
we  cannot  speak  so  definitely.  The  initial  dose  should 
always,  as  we  have  already  indicated,  be  small.  The 
drug  should  be  increased  after  some  days  or  weeks, 
and  it  should  be  regarded  as  a  failure  of  technique 
if  the  prescriber  ever  has  to  reduce  the  dose  owing  to 
commencing  with  too  large  a  quantity.  He  should, 
so  to  speak,  feel  his  way,  looking  carefully  for  the 
changes  which  will  show  that  the  drug  is  doing  its 
work.  The  temperature  will  approximate  to  normal 
almost  from  the  first,  certainly  as  the  circulation 
feels  the  result  of  the  additional  thyroid  extract. 
The  pulse  will  increase  in  rate,  and,  if  charted,  will 
show  a  steady  approximation  to  the  normal.  It  must 
be  remembered  that  these  patients  are  often  small, 
and  that  small  people  have,  under  normal  conditions, 
a  more  rapid  pulse  than  large  individuals.  When  we 
find,  therefore,  that  a  small  patient  has  a  slow  pulse, 
we  should  seek  for  the  reason.  Again,  the  subjective 
symptoms  will  improve  under  thyroid  medication; 
the  feelings  of  languor,  the  extreme  chilliness,  the 
depression,  and  the  general  discomfort,  will  (hminish 
in  severity. 

Provided  that  such  changes  are  looked  for  and  noted 
as  they  appear,  it  will  be  safe  to  increase  the  dose 
should  they  be  delayed  or  incomplete.  The  adminis- 
tration of  thyroid  is  both  an  art  and  a  science:  an 
art,  because  of  the  skill  required  to  apply  correctly 


126   THE  OEGANS  OF  INTERNAL  SECRETION 

the  knowledge  gained  of  thyroid-therapy;  and  a 
science,  because  of  the  exactitude  of  such  application, 
which  is  essential  if  we  wish  to  achieve  the  best  results. 

In  cases  of  submyxcedema,  it  is  far  better  to  err 
on  the  side  of  caution — i.e.,  of  too  small  doses — than 
of  rashness.  The  former  can  be  remedied  as  the 
reaction  of  the  patient  indicates;  while  the  latter  may 
not  only  lose  the  faith  of  the  patient  in  tins  remedy 
(which  is,  if  the  diagnosis  be  correct,  the  only  remedy), 
but  may  even  make  the  prescriber  doubt  his  own  judg- 
ment. One-tenth  to  one-quarter  of  a  grain  should 
form  an  initial  dose,  certainly  in  the  majority  of  cases, 
which,  when  all  is  said  and  done,  are  in  the  main  minor 
degrees  of  deficiency.  This  may  be  given  two  or  three 
times  a  day,  and  increased  to  J  grain,  1  grain,  or  even 
2  grains,  three  times  a  day.  Generally  speaking,  this 
is  quite  a  sufficiently  large  dose.  There  are  cases  of 
submyxoedema  which  require  larger  doses,  but  they 
should  only  attain  to  these  after  a  long  administration. 

One  other  word  of  warning,  and  we  may  conclude. 
The  prescriber  must  be  able  to  rely  upon  his  prepara- 
tion. He  must  know  that  the  percentage  composition 
is  constant,  that  it  contains  a  due  proportion  of 
iodine,  and  that  it  is  fresh  and  has  not  reposed  on  a 
shelf  in  a  local  chemist's  shop  for  many  moons. 
Thyroid  extract  degenerates,  and  when  this  happens 
it  becomes  inert;  and  it  does  not  take  long  for  this 
to  happen.  If  the  patient  fails  to  react,  we  must 
remember  that  the  quality  of  the  drug  may  be  at 
fault,  and  not  the  diagnosis.     So  long  as  the  drug  is 


THYEOID  DEFICIENCY  127 

fresh,  it  matters  little  whether  it  be  given  in  the  form 
of  dry  extract,  liquid  extract,  or  one  of  the  many 
prettier  preparations  on  the  market.  The  prescriber 
must  know  what  he  is  prescribing,  or  he  will  be  unable 
properly  to  check  progress. 

Finally,  as  the  treatment  proceeds,  a  careful  watch 
must  be  kept  upon  the  temperature,  pulse,  and  weight, 
for  mainly  on  these  points  can  the  supply  of  thyroid 
extract  be  regulated. 

References. 

1  Chapter  XIII.,  p.  192. 

2  Practitioner,  vol.  xciv.,  No.  1,  p.  30. 

3  The  Newer  Physiology  in  Surgical  and  General  Practice,  by 
Rendle  Short,  p.  85. 

4  Practitioner,  vol.  xciv.,  No.  1,  pp.  40,  41. 

5  Hertoghe  quotes  Murray  in  saying  that  these  patients  show 
a  marked  disinclination  to  discuss  these  symptoms,  and  asks 
whether  this  is  due  to  the  fact  that  such  hallucinations  show  a 
marked  resemblance  to  those  associated  with  alcoholism.  They 
are  due,  Hertoghe  believes,  to  infiltration  of  the  nervous  centres, 
or  to  more  local  infiltration,  such  as  thickening  of  the  aural 
mucosa,  Eustachian  tubes,  and  the  naso-pharynx. 

6  In  niyxcedenia  Bran  and  Mott  have  shown  the  presence  of 
subacute  general  chromatolysis  of  nerve  cells. 

7  Chronic  Intestinal  Stasis. 


CHAPTBE  VI 
THE  PITUITARY  BODY 

The  existence  of  this  body  has  been  known  for 
centuries,  but  until  recently  it  has  been  regarded  as 
of  no  functional  importance — as  a  vestigial  relic. 
Now,  however,  the  very  reverse  has  been  shown  to 
be  the  case,  and  since  1895  it  has  been  known  that 
this  small  gland  exerts  an  active  influence  upon  the 
general  bodily  metabolism.  Its  intimate  functions 
are  still  far  from  clear,  and  experiments  have  not 
infrequently  led  to  contrary  results.  However,  the 
light  is  beginning  to  dawn,  and  clinicians  are  now 
reaping  the  benefits  which  laboratory  workers  have 
made  possible  by  their  investigations  of  the  structure 
and  functions  of  this  gland. 

These  investigations  have  been  made  largely  with 
a  view  to  ascertain  the  results  of  extirpation  experi- 
ments, and  the  conclusion  arrived  at  is  this,  that,  far 
from  being  a  vestigial  remnant  and  unnecessary  to 
life,  its  influence  upon  the  health  is  of  prime  impor- 
tance, and  that  its  normal  functioning  is  essential  to 
health. 

Its  full  relation  to  bodily  efficiency  has  still  to  be 
explained,   as  there   are  aspects  and  features   about 

128 


THE  PITUITARY  BODY  129 

which  we  should  like  more  enlightenment.  The 
French  were  wont  to  refer  to  the  pituitary  as  "  l'organ 
enigmatique,"  and  its  mysteries  more  than  justify 
such  a  name.  The  ancients,  while  cognizant  of  its 
existence,  regarded  it  from  a  different  standpoint. 
Thus,  Galen  and  Vesalius  believed  that  it  was  con- 
cerned in  the  formation  of  the  nasal  secretion;  hence 
the  name  "  pituitary."  Vieussens  and  Sylvius  con- 
sidered that  it  was  concerned  with  the  manufacture 
of  the  cerebro-spinal  fluid.  The  first  hint  as  to  its 
real  functions — namely,  the  manufacture  of  an  internal 
secretion — is  conveyed  in  a  paper  to  which  Cushing 
calls  attention.  This  was  written  by  Lower,  and  was 
called  "  Dissertatio  de  Origine  Catarrhi,"  167*2,  and 
contained  the  statement:  "For  whatever  serum  is 
separated  into  the  ventricles  of  the  brain  and  tissues 
out  of  them  through  the  infundibulum  to  the  glandula 
pituitaria  distills  not  upon  the  palate,  but  is  poured 
again  into  the  blood  and  mixed  with  it."  Here, 
then,  we  have  the  precursor  of  our  knowledge  of 
an  internal  secretory  organ. 

Structure  o£  the  Pituitary  Body. 

The  pituitary  body  consists  of  three  parts:  an 
anterior  part  (glandular),  an  intermediate  portion, 
and  a  posterior  or  nervous  part.  The  anterior  part 
is  composed  of  a  network  of  epithelial  cells,  between 
which  run  many  wide  bloodvessels  with  thin  walls. 
This  part  of  the  gland  is  derived  from  the  buccal 
invagination    (that    portion    known    as    "  Rathke's 

9 


130   THE  ORGANS  OF  INTERNAL  SECRETION 

pouch  ").  As  Swale  Vincent  points  out,  the  structure 
is  similar  to  the  adrenal  cortex,  the  islets  of  Langerhans, 
the  thyroid,  the  thymus  (in  its  epithelial  stage),  and 
the  interstitial  tissue  of  the  ovary  and  testis.1  Next 
to  this  anterior  part  comes  the  pars  intermedia,  which, 
while  it  is  derived  from  Rathke's  pouch,  and  resembles 
the  pars  glandularis  in  structure,  differs  from  it  in 
that  "its  cells  are  less  glandular  and  its  bloodvessels 
much  less  numerous."2  This  portion  of  the  gland  is 
separated  from  the  pars  anterior  by  a  well-defined 
cleft;  but  it  is  not  always  markedly  separate  from 
the  pars  posterior.  This  latter  portion  of  the  gland 
is  derived  from  the  infundibulum,  or  stalk  of  the 
pituitary.  This  is  attached  by  its  terminal  portion 
to  the  floor  of  the  third  ventricle;  while  its  other 
extremity  expands  and  forms  the  posterior  part  of  the 
pituitary  body.  This  is  known  as  the  pars  nervosa, 
and  consists  of  neuroglial  fibres  and  cells. 

Histologically  the  anterior  part  of  the  gland  consists, 
as  already  stated,  of  "  trabecular  masses  of  epithelium- 
like cells  between  which  are  very  numerous  sinus-like 
blood-capillaries  lying  in  intimate  relation  to  the  cells, 
which  are,  indeed,  sometimes  set  closely  round  the 
blood-spaces."3  This  is  the  largest  part  of  the  gland, 
and  likewise  the  most  freely  supplied  with  blood.  It 
is  supplied  "  by  eighteen  to  twenty  small  arterioles 
which  converge  towards  the  infundibulum  from  the 
circle  of  Willis  and  pass  into  it  along  the  stalk  "  (Dandy 
and  Goetsch).4  This  part  of  the  gland,  therefore,  is 
one  of  the  most  vascular  parts  of  the  body. 


THE  PITUITAKY  BODY  131 

There  are  two  varieties  of  cells  in  this  part  of  the 
pituitary:  clear,  non-staining,  and  granular,  staining 
cells,  the  latter  being  divided  into  oxyphil  and  basophil. 
In  some  animals  all  the  cells  are  set  like  a  columnar 
epithelium  round  blood-sinuses  (Schafer).  It  is  in- 
teresting to  note  that  in  pregnancy  large  granular  cells 
are  present  in  unusual  numbers,  and  have  been  called 
pregnancy  cells. 

The  pars  intermedia  resembles  the  pars  anterior  in 
general  formation,  but  its  cells  are  less  granular  and 
it  is  not  so  vascular.  There  is  no  sharp  line  of  de- 
marcation between  the  pars  anterior  and  the  pars 
intermedia,  but  they  are  distinguished  by  the  character 
of  the  cells.  Behind  the  inter  glandular  cleft  "  the  pars 
intermedia  forms  a  well-marked  layer  of  varying  depth ; 
it  also  extends  as  a  thin  stratum  over  the  surface  of  the 
pars  nervosa,  as  well  as  over  the  neck  of  the  gland  which 
connects  the  pars  nervosa  with  the  inf undibulum. "  * 

But  the  pars  intermedia  is  not  everywhere  sharply 
marked  off  from  the  pars  nervosa,  for  strands  of  cells 
may  extend  a  variable  distance  between  the  fibres  of 
the  pars  nervosa.  The  granular  and  hyaline  globules, 
which  are  present  in  this  part  of  the  pituitary,  pass 
into  the  pars  nervosa  and  can  be  traced  as  far  as  the 
;'  continuation  of  the  third  ventricle  into  the  stalk." 
Herring  concludes  that  the  hyaline  and  granular  sub- 
stances produced  by  breaking  down  of  the  cells  of  the 
pars  intermedia  form  a  secretion  which  finds  its  way 
into  the  cerebro-spinal  fluid.  There  seems  little  doubt, 
*  Schafer,  "The  Endocrine  Organs,"  p.  80. 


132  THE  ORGANS  OF  INTERNAL  SECRETION 

however,  that  the  pars  anterior  forms  a  substance 
which  has  a  marked  action  on  metabolism,  but  so  far 
no  active  principle  has  been  isolated  from  this  part  of 
the  gland.  The  physiological  effects  of  extracts  of  the 
posterior  lobe  are,  as  we  have  seen,  definite  and  striking. 
The  'pars  'posterior  or  pars  nervosa  is  formed  almost 
entirely  of  neuroglial  fibres,  with  neuroglial  cells 
scattered  between  the  fibres.  Between  these  fibres  is 
found  a  hyaline  matter,  which  is  more  abundant  in 
the  neighbourhood  of  the  stalk.  Schafer  maintains 
that  there  can  be  little  doubt  that  the  activity  of 
extracts  of  this  part  of  the  gland  is  due  to  this  substance. 
Herring  denies  that  any  nerve  cells  are  present  in 
the  pars  posterior,  and  there  are  very  few  nerve 
fibres. 

Physiological  Functions. 

In  studying  the  physiological  action  of  extracts 
of  the  pituitary,  we  are  faced  with  certain  apparent 
contradictions.  If  an  extract  of  the  whole  gland  be 
injected,  there  is  an  immediate  rise  of  blood-pressure, 
associated  with  a  slowing  of  the  heart's  action.  In 
this  connection  the  effect  of  pituitary  is  similar  to 
that  produced  by  adrenin.  The  arterial  system  is 
affected  by  this  extract,  as  is  all  the  involuntary 
tissue  of  the  body — in  other  words,  vaso-constriction 
is  increased;  and  it  is  this  property  which  makes 
pituitary  extract  such  a  valuable  remedy  in  shock. 
We  shall  refer  to  this  factor  when  discussing  the 
therapeutic  aspect  of  extracts  of  the  pituitary  body. 


THE  PITUITAKY  BODY  133 

Certain  observers  believe  that  the  substance  which 
exerts  this  tonic  action  exists  in  the  posterior  part 
of  the  gland  only6  (which  includes  in  this  connection 
the  pars  intermedia  as  well  as  the  pars  nervosa),  and, 
in  point  of  fact,  it  has  been  shown  that  this  effect 
is  produced  by  either  the  pars  intermedia  or  the  pars 
posterior,  but  more  by  the  latter  than  by  the  former. 

As  well  as  this  tonic  effect  upon  the  heart  and  the 
bloodvessels  (which,  while  it  resembles  that  produced 
by  adrenin,  differs  from  it  in  that  this  latter  extract 
causes  increase  in  the  rapidity  of  the  heart's  beat, 
whereas  pituitary  extract  causes  slowing  of  the  pulse), 
pituitary  extract  acts  upon  other  plain  muscle,  such 
as  the  stomach,  the  intestines,  the  uterus,  and  the 
bladder. 

As  opposed  to  this  general  stimulation,  there  are 
one  or  two  notable  exceptions.  The  kidney,  when 
stimulated  by  the  administration  of  extract  of  the 
pituitary,  reacts  in  a  different  manner.  Thus,  the 
renal  arteries  dilate,  there  is  diuresis,  and  this  is 
partly  due  "to  a  selective  influence  of  one  of  the 
contained  hormones  upon  the  cells  of  the  renal  tubules. 
.  .  .  This  action  has  been  supposed  to  be  due  to 
a  special  diuretic  hormone  from  the  pars  intermedia, 
and  it  is  not  as  yet  certain  that  this  is  not  the  case; 
but  it  seems  more  probable  that  all  the  effects  that  it 
causes  are  due  to  the  active  principles  of  the  posterior 
lobe."6 

Again,  the  effects  produced  upon  lactation  by 
injections    of    tins    gland    are    interesting.     Ott    and 


134  THE  OKGANS  OF  INTEENAL  SECRETION 

Scott,  in  1910-11,  pointed  out  that  it  possessed  a 
marked  galactagogue  action,  and  since  that  time  many 
observers  have  supported  this  statement.  There  have, 
however,  been  a  few  dissentients,  who  maintain  that 
extracts  of  pituitary  have  no  such  effect;  these  are, 
however,  in  the  minority.* 

Weed  and  Cushing  have  shown  that  extracts  of  the 
pars  posterior  produce  a  stimulation  of  the  flow  of 
cerebro-spinal  fluid,  which  appears  not  to  be  dependent 
upon  a  rise  of  blood-pressure. 

One  other  feature,  which  at  first  sight  appears 
rather  contradictory,  is  the  effect  of  pituitary  extract 
upon  amenorrhcea.  It  has  been  on  several  occasions 
utilized  to  counteract  cessation  of  menstruation,  and 
with  marked  success.  This  is,  of  course,  contrary  to 
what  we  should  expect,  but  can  only  be  explained,  as 
suggested  by  Harrower,  on  the  assumption  that  the 
gland  is  acting  vicariously  in  carrying  on  this  function. 
It  is  known  that  the  pituitary  undergoes  hypoplasia 
during  pregnancy,  and  Fromme  tried  injecting  an 
extract  of  the  gland  in  amenorrhcea,  with  some  degree 
of  success. 

Now  as  regards  the  active  principles  of  the  pituitary. 
First  of  all  in  importance,  certainly  from  the  thera- 
peutic standpoint,  is  the  fact  that  the  majority  of 
observers  are  agreed  that  the  posterior  part  of  the 

*  Schafer  maintains  that  the  effect  of  pituitary  extract  upon 
lactation  is  one  of  the  most  striking  experiments  in  physiology; 
but  Heaney  does  not  believe  in  the  galactogogic  effect  of  pituitary 
extract  (quoted  in  Harrower's  "  Practical  Hormone -Therapy  "). 


THE  PITUITAEY  BODY  135 

gland  contains  the  active  principle.  Therapeutically, 
better  and  more  constant  results  have  been  obtained 
by  the  use  of  some  preparation  of  this  part  of  the 
gland  than  by  the  exhibition  of  extracts  of  the  whole 
gland  or  by  the  attempted  isolation  of  extracts  of  the 
other  portions;  although,  as  we  shall  see,  extracts  of 
the  anterior  lobe  have  their  therapeutic  uses.  Harrower 
states  that  a  definite  salt  has  been  isolated  from  the 
pituitary — hypophysin  sulphate — which  is  available  for 
use,  and  standardized  in  1  in  1,000  solutions.  This 
has  been  utilized  by  many  observers,  who  report 
favourably  on  its  use  (Hertzberg,  Fuhner,  and  Har- 
rower). 

The  Effects  Produced  by  Disease  of  the  Pituitary 

Body. 

In  discussing  the  thyroid  gland,  we  saw  that  morbid 
conditions  due  to  its  faulty  functioning  might  be 
classified  into  those  due  to  hypersecretion  (hyper- 
thyroidism), and  those  due  to  deficient  secretion 
(hypothyroidism).  In  like  manner,  when  discussing 
diseases  due  to  abnormal  working  of  the  hypophysis 
cerebri,  we  may  adopt  this  division — namely,  diseases 
due  to  excessive  action  of  the  pituitary  and  those  due 
to  deficiency. 

The  best  recognized  disease  associated  with  this 
gland  is  that  to  which  Marie  gave  the  name  "  acro- 
megaly "  {ciKpov— point;  p£ya9=l8rge).  It  is  now 
believed  that  this  condition  owes  its  origin  to  a  hyper- 
secretion of  the  pituitary,  and  that  part  of  the  symp- 


136   THE  OEGANS  OF  INTERNAL  SECRETION 

toms  are  directly  due  to  an  excess  of  the  hormone 
elaborated  by  the  anterior  part  of  this  gland.*  It  is 
also  now  generally  believed  that  a  common  sequence 
in  the  production  of  this  disease  is  a  primary  hyper- 
pituitarism, the  cause  of  which  may  or  may  not  be 
clear,  followed  in  some  cases  by  a  hypopituitarism. 

Before  proceeding  to  outline  the  features  of  these 
two  clinical  conditions,  we  will  briefly  describe  the 
symptoms  of  acromegaly.  This  disease  usually  com- 
mences with  a  marked  narrowing  of  the  field  of  vision, 
so  that  ocular  symptoms  are  a  prominent  part  of  the 
complaint  in  its  early  stages.  This  feature  may  be 
due  to  the  presence  of  a  tumour  in  the  gland  pressing 
upon  the  region  of  the  optic  chiasma.  Sooner  or 
later  are  developed  the  characteristic  features  of  the 
complaint  which  caused  Marie  to  describe  it  under 
the  name  "  acromegaly/'  These  consist  in  a  marked 
overgrowth  of  the  head  and  extremities.  The  face 
enlarges  and  coarsens  in  its  expression ;  while  the  shape 
of  the  head  tends  to  alter,  becoming  flatter  and  squarer. 
The  fingers,  if  viewed  by  the  X-rays,  show  an  enlarge- 
ment of  the  bones,  with  a  "  mushrooming  "  of  the 
terminal  phalanges.  The  entire  skeleton  increases  in 
size,  so  that  the  individual  becomes  more  or  less 
generally  enlarged. 

Certain  other  changes  are  common,  and  these   de- 

*  Schafer  says:  "  That  the  acromegalic  skeletal  growth  is 
produced  by  hypertrophy  and  over-secretion  of  the  anterior 
lobe  is  highly  probable,  both  as  the  result  of  partial  extirpations 
in  animals  and  from  the  effect  of  operative  removal  of  pituitary 
tumours  in  man  "  ("  The  Endocrine  Glands/5  p.  113). 


THE  PITUITABY  BODY  137 

velope  concurrently  with  the  skeletal  enlargement. 
There  is  a  tendency  to  hypertrichosis,  with  a  general  in- 
crease of  the  hair  all  over  the  body.  Sexual  activity 
diminishes,  as  a  rule,  early  in  the  course  of  the  disease : 
although,  in  those  cases  where  hyperpituitarism  is 
succeeded  by  hypopituitarism,  sexual  activity  may 
be  primarily  increased,  and  subsequently  diminished. 
A  tendency  to  glycosuria  is  common,  which,  again, 
may  be  followed  by  a  diminished  glycogenesis.  The 
integument  is  also  thickened,  in  a  somewhat  similar 
manner  to  that  seen  in  myxcedema;  while  if  the 
disease  commences  before  ossification  of  the  epiphyses 
has  taken  place,  the  stature  becomes  enormous  and  the 
individual  turns  into  a  giant. 

It  is  now  generally  believed  that  acromegaly  is  due 
to  an  overgrowth  of  the  pituitary;  indeed,  in  many 
cases  actual  tumours  are  present,  and  have  been  demon- 
strated post  mortem.  Sometimes,  in  these  cases, 
the  sella  turcica  can  be  shown  by  a  skiagram  to  be 
definitely  enlarged.  On  the  other  hand,  after  the 
glandular  enlargement,  a  secondary  atrophy  may  ensue, 
in  which  case  the  symptoms  become  those  of  hypo- 
pituitarism. It  is  at  this  stage  that  symptoms  contra- 
dicting the  earlier  clinical  picture  may  make  their 
appearance,  so  that,  whereas  at  first  there  may  have 
been  a  tendency  to  undue  glycogenesis,  there  is  now 
increased  sugar  storage,  and  whereas  at  first  there  had 
been  hypertrichosis,  there  is  now  a  change  in  the  hair, 
the  distribution  often  tending  towards  the  feminine 
type. 


138  THE  OKGANS  OF  INTERNAL  SECRETION 

Again,  it  does  not  follow  that  every  case  of  what 
Cushing  calls  dyspituitarism  may  commence  as  a 
hyperpituitarism,  and  subsequently  change  to  a  hypo- 
pituitarism; for  some  cases  evidence  symptoms  point- 
ing to  the  latter  condition  from  the  first.  The  state 
described  by  Frohlich,  and  named  by  Bartels 
11  Dystrophia  adiposogenitalis,"  is  essentially  a  typical 
example  of  hypopituitarism.  The  symptoms  pointing 
to  this  state  are,  as  is  to  be  expected,  the  opposite  of 
those  typical  of  hyperpituitarism.  Thus,  the  stature 
is  small  (if  the  disease  commences  before  adolescence), 
adiposity  is  excessive,  sexual  development  is  delayed 
or  deficient,  the  development  of  hair  is  wanting,  and 
there  is  a  tendency  to  the  formation  of  feministic 
characteristics.  Thus,  the  hair  on  the  pubes  is  more 
localized  than  is  the  case  in  man,  but  the  development 
of  the  hair  on  the  head  is  frequently  abundant.  The 
sweat  is  usually  deficient,  although  the  skin  exhibits 
a  smooth  and  even  texture. 

Cushing  deals  very  fully  with  the  production  of  this 
state  in  his  book,  "  The  Pituitary  Body  and  its  Dis- 
orders." He  believes  that  the  tendency  to  the  deposi- 
tion of  fat,  which  subjects  of  hypopituitarism  show, 
owes  its  origin  to  deficiency  of  the  secretion  from  the 
posterior  lobe.  Likewise  the  unusually  high  tolerance 
for  sugar  and  the  increased  assimilation  of  carbo- 
hydrates are  due  to  the  same  cause. 

Again,  in  hypopituitarism  there  are  other  changes 
which  may  be  expected  in  the  symptoms.  The  tem- 
perature is   usually  subnormal,  the   pulse  slow,   the 


THE  PITUITAEY  BODY  139 

blood-pressure  low,  and  the  mental  attitude  sluggish, 
with  a  tendency  to  somnolence.  It  will  be  seen  that 
the  clinical  picture  is  not  unlike  that  seen  in  myx- 
cedema.  The  parallel  is,  in  fact,  a  close  one,  certainly 
in  many  features. 

McKennan,  in  speaking  of  epilepsy,  states  that,  from 
the  study  of  radiograms  and  from  the  evidence  of  the 
post-mortem  room,  the  pituitary  gland  is  often  found 
to  be  at  fault  in  this  disorder.  He  believes  that 
pituitary  administration  should  go  hand-in-hand  with 
the  prescription  of  the  bromides,  the  latter  being 
gradually  reduced  in  dosage,  but  the  patient  main- 
taining the  pituitary  treatment  for  a  lengthy 
period. 

It  is  important  to  remember  that  the  symptoms  of 
hypopituitarism  will  differ  according  to  whether  the 
deficiency  first  appears  before  adolescence,  or  is  only 
in  action  after  adult  life  has  commenced.  Once  the 
ossification  of  the  epiphyses  has  taken  place,  there  is 
no  possibility  of  further  increase  of  stature.  But  the 
increase  in  the  integuments,  the  alteration  in  the  circu- 
lation, the  changes  in  the  mental  outlook — these  all 
point  to  the  underlying  cause.  Schafer  says  that  the 
symptoms  differ  widely,  according  to  whether  the  an- 
terior or  posterior  lobe  of  the  gland  is  mainly  affected; 
if  the  lesion  is  concerned  with  the  anterior  part 
of  the  pituitary,  the  chief  effects  will  be  upon  the 
stature,  while  affections  of  the  posterior  lobe  produce 
fat  formation  and  deficient  sexual  development. 
A    deficiency   of   the    pituitary    secretion,    appearing 


140   THE  OKGANS  OF  INTEENAL  SECRETION 

during  childhood,  would  produce  a  dwarfed  stature,* 
marked  adiposity,  delayed  sexual  development,  with 
absence  of  the  secondary  sexual  characteristics.  The 
pubic  hair,  in  the  male,  is  confined  to  the  pubic  region, 
and  does  not  extend  towards  the  umbilicus,  while  there 
are  other  signs  of  feminism  present.  The  extremities 
tend  to  be  more  rounded,  there  is  some  degree  of  genu 
valgum,  a  broad  pelvis,  and  sometimes  a  well-marked 
mammary  development.  The  skin  is  smooth  and  the 
nails  are  small  and  do  not  show  the  usual  crescents 
at  their  bases.  It  is  possible  that  with  one  part  of 
the  gland  functioning  adequately,  and  the  other 
deficient,  the  clinical  picture  might  correspond  to 
what  is  expected  when  the  particular  part  is  abnormal. 
Supposing  the  anterior  part  of  the  gland  to  be  normal 
and  the  posterior  deficient,  we  should  expect  a  fully- 
grown  individual,  but  with  excessive  deposits  of  fat, 
slow  circulation,  sluggish  mentality,  and  the  other 
features  of  hypopituitarism,  with  the  exception  of 
stunted  skeletal  development. 

Although  much  of  this  particular  study  leads  us 
into  realms  of  speculation,  nevertheless  there  is  strong 
probability  that  these  suppositions  are  near  the  truth. 
Although  the  pituitary  is  by  no  means  always  atrophied 
in  dwarfs,  this  is  not  tantamount  to  saying  that  its 
secretion  is  normal  qualitatively  as  well  as  quantita- 
tively; for  it  might  be  enlarged  by  tumour  formation,  or 
by  hypertrophy,  without  secreting  the  normal  amount. 

*  Cases  have  been  recorded  in  which  the  pituitary  gland  has 
been  found  atrophied  in  dwarfs,  although  this  is  not  invariable. 


THE  PITUITARY  BODY  141 

Here  we  must  leave  the  discussion  of  abnormalities 
in  the  pituitary  secretion,  and  discuss  briefly  the  treat- 
ment of  such  disorders. 


Treatment  of  Pituitary  Disorders. 

In  a  brief  review  of  the  treatment  of  pituitary  dis- 
orders, or,  rather,  of  such  disorders  as  come  within  the 
scope  of  this  chapter,  we  must  perforce  spend  some  time 
on  the  study  of  both  surgical  and  medical  treatment. 
For,  as  regards  that  class  of  disorder  which  is  caused 
by  a  radical  change  in  the  structure  of  the  gland  or 
by  a  tumour  interfering  with  the  adequate  functioning 
of  the  gland  either  by  direct  pressure,  or  by  raising 
the  intracranial  tension,  surgery  is  not  always  even 
a  matter  of  choice,  but  a  matter  of  necessity. 

As  we  have  already  said,  some  cases  of  acromegaly 
have  shown  the  existence  of  tumours  of  the  pituitary 
gland  which  have  upset  its  normal  secretion.  Thus, 
a  cystic  growth  of  the  gland,  when  removed,  may  pro- 
duce hypopituitarism,  which,  again,  can  be  remedied  in 
some  cases  by  pituitary  feeding.  But  previous  to  the 
operative  measures  the  symptoms  have  naturally  been 
those  of  excessive  secretion,  sometimes  accompanied  by 
localizing  symptoms  due  to  an  increase  of  intracranial 
tension. 

Gushing  has  reviewed  the  treatment  of  pituitary 
disorders  very  fully  in  his  book,7  and  he  deals  with 
the  question  of  surgical  interference  and  with  the 
choice  of  treatment  in   a  thorough  manner.     Apart 


142   THE  ORGANS  OF  INTERNAL  SECRETION 

from  those  cases  which  show  the  presence  of  a  tumour, 
where  surgical  treatment  is  generally  the  only  hope  at 
the  present  state  of  our  knowledge— i.e.,  with  the 
uncertainty  of  the  minutiae  of  the  diagnosis — we  can 
scarcely  recommend  surgical  interference  for  hyper- 
pituitarism, on  the  same  grounds  on  which  some 
authorities  recommend  partial  removal  of  the  thyroid 
gland  for  hyperthyroidism.  In  this  connection  Cushing 
says: 

"  In  view  of  the  fact,  therefore,  that  hyperpitui- 
tarism, so  far  as  glandular  secretion  is  concerned,  is  a 
condition  which  tends  to  right  itself,  it  must  remain 
for  the  time  being  a  matter  of  uncertainty  as  to 
whether  or  not,  in  the  absence  of  a  degree  of  hyper- 
plasia sufficient  to  cause  neighbourhood  symptoms, 
operative  measures  can  hold  out  any  promise  of  per- 
manently controlling  the  disorder. 

"  When,  however,  neighbourhood  symptoms  have 
arisen  owing  to  the  extreme  enlargement  of  the  gland, 
due  to  the  formation  of  an  adenomatous  struma, 
whether  or  not  there  have  been  antecedent  symptoms 
of  acromegaly,  the  surgical  aspects  of  the  matter  stand 
on  firmer  ground."8 

Owing  to  the  situation  of  the  pituitary  gland,  and 
the  difficulty  of  operation,  we  see,  therefore,  that  its 
partial  removal,  in  the  absence  of  urgent  symptoms,  is 
not  to  be  considered,  even  as  a  possibility,  in  the  hope 
of  benefiting  symptoms  of  hyperpituitarism.  Fortu- 
nately, there  seems  to  be  a  good  deal  of  evidence  to 
point  to  the  assumption  that  states  of  hypersecretion 


THE  PITUITARY  BODY  148 

are  often  transitory,  so  that  we  must  treat  the  early 
stages  of  such  a  condition  with  care  and  watchfulness. 
It  is  opposed  to  our  present  knowledge  to  administer 
extract  of  the  pituitary  gland  to  patients  suffering 
from  acromegaly;  for  as  thyroid  extract  makes  patients 
suffering  from  Graves'  disease  worse,  so  does  pituitary 
extract  affect  acromegalics.9  The  subsequent  hypo- 
pituitarism may  well  be  met  by  organo-therapy;  some- 
times, indeed,  one  feels  tempted  to  employ  the  extracts 
of  other  of  the  endocrine  glands  in  the  treatment  of 
hyperpituitarism,  in  the  hope  that  the  hormone  balance 
will  be  restored.  In  the  present  state  of  our  know- 
ledge, however,  this  latter  form  of  therapy  for  this 
disorder  must  needs  be  empirical;  nevertheless,  much 
has  in  the  past  been  achieved  by  empiricism,  and 
doubtless  in  the  future  much  more  will  have  to  be 
placed  to  its  credit. 

Turning  now  to  the  study  of  the  treatment  of  hypo- 
pituitarism, we  find  that  medicine  naturally  takes  a 
more  prominent  place  than  surgery.  The  administra- 
tion of  pituitary  substance  may  be  carried  out  in  three 
ways — namely,  by  ingestion,  by  injection,  or  by  graft- 
ing. For  simplicity  of  administration,  the  first  is  un- 
doubtedly the  method  of  choice,  and  consequently  is 
the  one  mainly  relied  upon  in  actual  practice.  From 
the  experimental  standpoint,  Goetsch  found  that  the 
subcutaneous  injection  of  the  extract  in  dogs  was  more 
effective  in  the  ratio  of  4  to  1  than  the  oral  administra- 
tion, while  the  intravenous  injection  was  even  more 
effective  than  the  subcutaneous  in  the  ratio  of  2  to  1. 


144   THE  ORGANS  OF  INTERNAL  SECEETION 

These  tests  were  made  with  the  standard  devised  by 
Cushing,  from  whose  book  they  are  quoted.  This 
standard  is  based  upon  the  increased  tolerance  lor 
sugar  which  patients  suffering  from  hypopituitarism 
exhibit:  for  in  hypopituitarism  "the  rational  dosage 
of  glandular  extract  to  be  administered  by  mouth  can 
possibly  be  determined  by  giving  the  individual  daily 
an  amount  of  glucose  or  lsevulose  sufficient  to  produce 
a  temporary  mellituria  in  a  normal  individual  of  equal 
bodily  weight;  meanwhile  an  increasing  amount  of  the 
extract  is  administered  daily,  until,  imder  the  condi- 
tions of  increased  carbohydrate  tolerance  which  the 
patient  exhibits,  hyperglycemia  occurs,  with  a  trace 
of  sugar  in  the  urine."10 

Having  arrived,  then,  at  the  diagnosis  of  hypopitui- 
tarism, we  next  have  to  decide  upon  the  treatment, 
both  as  to  the  method  to  adopt  and  as  to  the  particular 
preparation  to  employ.  We  are  concerned  here  more 
with  the  routine  administration  of  pituitary  extract  (in 
one  of  its  many  forms)  than  we  are  with  its  employ- 
ment in  urgent  conditions,  such  as  shock,  obstetrical 
emergencies,  etc. ;  so  that  this  account  must  be  under- 
stood to  deal  chiefly  with  the  treatment  of  definite 
hypopituitarism. 

Two  cases  in  which  preparations  manufactured 
from  the  anterior  lobe  were  employed  with  marked 
success  have  been  reported  by  Magnier.*  These  were 
cases  of  mental  deficiencj^;  in  one  instance  delayed,  in 
the  other,  arrested  mental  development. 

*  Medical  Press  and  Circular,  September  22,  1920,  p.  226. 


THE  PITUITARY  BODY  145 

The  first  patient  was  a  child,  eight  years  of  age,  who 
came  under  treatment  for  mental  backwardness. 
There  was  obstinate  constipation  present.  He  was 
treated  with  one  2J-grain  tablet  daily  of  anterior  lobe 
pituitary  gland.  From  the  first  he  improved  markedly, 
the  intellect  became  much  brighter,  he  could  talk  and 
write,  and  the  bowels  became  regular.  The  author 
considers  that  the  natural  course  of  development  was 
delayed  by  an  attack  of  convulsions  as  a  child. 

The  second  patient  was  an  infant,  who,  at  the  age 
of  eighteen  months,  had  hardly  developed  since  his 
birth.  He  was  unable  to  sit  up,  took  no  notice  of 
outside  things,  and  had  an  idiotic  look.  The  same 
treatment  was  prescribed,  and  after  one  month  im- 
provement was  noted.  The  child  could  sit  up,  made 
attempts  to  crawl,  and  was  taking  food  well,  whereas 
previously  he  was  unable  to  take  any  food  except 
fluid. 

Both  these  patients  were  treated  by  anterior  lobe 
pituitary  gland  tablets  (Parke,  Davis  and  Co.),  and  the 
results  are  certainly  suggestive  of  the  help  which  can 
be  gained  by  pituitary  extract  in  cases  of  delayed 
development. 

An  interesting  note  by  Davidson  upon  the  value  of 
injections  of  pituitrin  is  to  be  found  in  the  British 
Medical  Journal  of  August  21,  1920.*  The  patient, 
an  ex-soldier,  was  admitted  to  hospital  "  with  a  history 
of  bronchitis  and  nephritis  (sic),"  contracted  on  the 

*  "The  Antidiuretic  Effect  of  Pituitary  Extract  in  Diabetes 
Insipidus." 

10 


146   THE  OEGANS  OF  INTEENAL  SECEETION 

Salonica  Front.  On  his  way  to  England  he  noticed 
polyuria  for  the  first  time.  In  hospital,  in  England, 
he  was  passing  just  over  300  ozs.  of  urine  in  the  twenty- 
four  hours.  Injections  of  pituitrin  were  given,  and 
these  produced  a  marked  fall  in  the  amount  of  urine 
passed.  Pituitary  extract  by  the  mouth,  however, 
had  no  such  action. 

This  case  is  quoted  as  it  is  an  example  of  the  relative 
merits  of  hypodermic  administration  and  injections. 
When  we  wish  to  get  a  specific  effect  upon  a  disorder 
such  as  diabetes  insipidus,  the  hypodermic  or  intra- 
muscular route  is  preferable. 

If  it  is  decided  that  pituitary  extract  is  required  over 
a  lengthy  period,  it  is  far  preferable  to  administer  it  by 
the  mouth,  as  there  are  many  disadvantages  attached 
to  both  the  other  methods.  Where  it  has  to  be  given 
repeatedly  by  injection,  the  intramuscular  method  is 
the  one  for  choice,  as  subcutaneous  injection  is  un- 
desirable on  account  of  the  local  anaemia  produced. 
For  a  very  rapid  result,  it  may  be  administered  by 
intravenous  injection  well  diluted  with  normal  saline 
solution. 

As  to  the  various  preparations  which  are  on  the 
market,  a  wide  selection  is  before  the  prescriber. 
Pituitrin  may  be  administered  by  hypodermic  or 
intramuscular  injection,  or  by  the  mouth.  The  dose 
in  the  latter  method  is  from  10  to  30  minims. 

This  preparation  is  said  to  be  especially  cardio-tonic 
in  action,  "  and  in  a  less  degree  hypertensive."11  Again, 
Hypophysin  (Fuhner)  is  stated  to  possess,  from  the 


THE  PITUITAEY  BODY  147 

physiological  standpoint,  "  the  essential  properties  of 
the  extract  of  the  macerated  posterior  lobe."12  These 
and  other  liquid  preparations  are  usually  put  up  in 
ampoules,  should  it  be  desired  to  administer  them 
hypodermically  or  intramuscularly.  The  dose  of  the 
liquid  preparations  is  usually  from  8  to  16  minims.  A 
preparation  which  will  be  found  useful  in  practice  is 
the  Elixir  Hypophysis  (Squire),  which  is  manufactured 
from  the  whole  gland,  1  teaspoonful  representing 
i  grain  of  the  dried  and  powdered  extract.  The  dose 
is  from  1  to  2  drachms  two  or  three  times  daily. 

Again,  pituitary  extract  is  manufactured  in  solid 
form,  either  as  a  separate  preparation  or  in  combina- 
tion with  other  of  the  endocrine  gland  extracts.  These 
products  are  very  numerous,  and  it  would  be  tedious 
to  mention  them  in  detail;  suffice  it  to  say  that  most 
of  the  wholesale  chemists  manufacture  such  extracts 
in  tablet  or  powder  form. 

It  is,  of  course,  as  important  in  dealing  with  this 
extract  as  it  is  in  dealing  with  thyroid  extract  that 
there  should  be  a  known  standard  of  strength,  and  that 
the  prescriber  should  be  sure  that  his  preparation  is 
fresh.  As  a  rule  this  is  easily  ascertained,  and  the 
dosage  regulated  with  some  degree  of  certainty. 

Many  manufacturers  place  on  the  market  prepara- 
tions specified  as  having  been  made  from  the  anterior 
or  posterior  part  solely,  and  thus  another  variety  of 
this  treatment  is  introduced.  The  majority  of  cases 
appear  to  indicate  treatment  with  posterior  extract; 
indeed,  the  majority  of  the  preparations  are  expressly 


148   THE  OKGANS  OF  INTEENAL  SECBETION 

stated  to  have  been  manufactured  from  the  pars 
posterior. 

Now  as  to  small  points  in  the  treatment  of  pituitary- 
disorders,  and  also  in  the  utilization  of  this  extract  in 
counteracting  symptoms.  First  in  importance  is  un- 
doubtedly its  contra-indication.  As  pituitary  extract 
raises  the  arterial  tension,  it  (or  any  preparation  con- 
taining it)  should  be  carefully  avoided  in  all  states 
indicating  hypertension.  It  should  be  administered 
with  caution  over  long  periods,  and  frequent  sphygmo- 
rnanometric  readings  taken  to  control  any  undue  rise 
in  blood-pressure.  The  present  writer  has  known  it 
work  wonders  in  some  neurasthenic  conditions,  like- 
wise in  states  of  weakness  following  long- continued 
strain,  in  impotence  and  such  disorders.  Again,  in 
delayed  convalescence,  in  persistent  low  blood-pressure, 
in  depressive  states,  and  the  like,  a  course  of  pituitary 
extract,  wisely  controlled,  will  frequently  be  found  to 
be  invaluable. 

The  requisite  dose  varies  enormously,  and  so  wide 
is  the  range  that  it  appears  probable  that  some  at 
least  of  the  failures  are  due  to  the  dose  being  unsuit- 
able. In  speaking  of  the  dosage  required  in  some  of 
these  cases,  Cushing  emphasizes  the  vast  range  of  dose 
which  is  effectual  in  different  cases.  Thus,  one  boy 
exhibiting  the  signs  of  hypopituitarism  in  a  marked 
manner  underwent  a  "  complete  mental,  moral,  and 
physical  awakening  "  by  taking  18  grains  of  whole 
gland  preparation  daily.  But  another  case  quoted  by 
the  same  author  required  as  much  as  300  grains  daily 


THE  PITUITARY  BODY  149 

(a  prohibitive  dose,  as  Cushing  remarks)  to  give  the 
same  subjective  benefits  which  other  patients  ex- 
perienced with  far  smaller  doses. 

In  undertaking  the  treatment  of  a  patient  by  means 
of  pituitary  extract,  it  is  wise  to  progress  slowly,  and 
to  endeavour  to  ascertain  the  dosage  required  by 
the  individual  case,  as  well  as  the  reaction  to  the 
extract.  In  practice,  it  is  often  necessary  to  rest 
content  with  methods  which  are,  perhaps,  not  so 
precise  as  those  which  are  open  to  laboratory  workers ; 
and  it  is  therefore  often  only  possible  to  watch  care- 
fully the  progress  made  under  the  treatment,  at  the 
same  time  looking  for  any  symptoms  the  amelioration 
of  which  may  justifiably  be  claimed  to  be  due  to  the 
drug. 

Cases  are  sometimes  encountered,  however,  especially 
in  neurasthenic  subjects,  in  which  irritability  is  pro- 
duced by  the  administration  of  pituitary  extract. 
Often  this  appears  to  be  due  to  the  rise  in  blood- 
pressure  which  follows  such  treatment;  but  it  is  well 
to  be  careful  to  reduce  the  dose  should  this  symptom 
appear,  or  even  to  cease  its  administration  altogether, 
and  after  a  few  days'  cessation  to  recommence  the 
treatment  with  small  doses.  This  will  generally  be 
successful  in  combating  the  irritability,  and  will  enable 
the  treatment  to  be  persevered  with  after  the  rest. 

In  Chapter  XIII.  the  use  of  pituitary  extract  in  com- 
bination with  other  organic  extracts  is  fully  discussed, 
also  the  joint  administration  of  this  substance  and 
thyroid  extract  is  considered. 


150   THE  ORGANS  OF  INTERNAL  SECRETION 

References. 

1  Swale  Vincent,  Practitioner,  vol.  xciv.,  No.  1,  p.  149. 

2  Schafer,  The  Endocrine  Glands,  p.  77. 

3  Ibid. 

4  Quoted  by  Schafer.  The  Endocrine  Organs,  p.  78. 

5  Howell,  Jour.  Exper.  Med.,  1898,  iii.  245-258. 

6  Harrower,  Practical  Hormone-Therapy,  p.  305. 

7  H.  Cushing,  p.  294  et  seq. 

8  Ibid. 

9  Experiments   of  Renon  and   Delile,  quoted   by  Cushing, 

p.  315. 

10  Cushing,  pp.  317,  318. 

11  Harrower,  p.  313. 
"  Ibid. 


CHAPTER  VII 
THE  ADRENAL  GLANDS 

The  study  of  the  chromaffin  system  involves  a  careful 
investigation  of  its  most  important  member — namely, 
the  adrenal  or  suprarenal  glands.  These  bodies  are 
now  known  to  possess  such  vital  properties  in  the 
body  physiology,  and  to  perform  such  an  indispensable 
part  in  the  maintenance  of  the  "  tonic  "  state  of  all  vas- 
cular and  plain  muscular  structures,  that  they' deserve 
a  foremost  place  in  any  study  of  the  endocrine  glands. 
Although  as  long  ago  as  the  sixteenth  century  the 
great  anatomist  Eustachius  discovered  the  existence 
of  the  adrenal  bodies,  their  importance  remained  un- 
known until  recent  years.  In  1849  Addison  discovered 
that,  in  some  cases  of  illness  characterized  by  definite 
pigmentation  of  the  skin,  the  adrenal  glands  were 
found  to  be  diseased,  often  with  a  tuberculous  in- 
fection. From  that  day  to  almost  fifty  years  after, 
our  knowledge  of  these  structures  may  be  said  to  have 
increased  but  little;  but  in  1894  the  famous  discovery 
by  Oliver  and  Schafer,  that  extracts  of  the  glands 
possessed  a  marked  blood-pressure-raising  property, 
inaugurated  the  interest  which  has  led  to  the  really 
remarkable  discoveries  of  the  properties  which   the 

151 


152   THE  ORGANS  OF  INTERNAL  SECRETION 

chromaffin   system   in    general,  and  the  adrenals  in 
particular,  possess. 

Before  commencing  the  study  of  the  therapeutic 
value  of  extracts  of  the  adrenals,  we  must  briefly 
outline  our  knowledge  of  these  glands,  both  from  the 
anatomical  and  physiological  standpoint. 


Anatomy  and  Physiology  of  the  Adrenal  Glands. 

The  suprarenal  glands  are  two  flattened  bodies  more 
or  less  globular  in  shape,  of  a  yellowish  colour,  and  are 
situated  behind  the  peritoneum  in  front  of  the  upper 
part  of  each  kidney.  Their  size  in  normal  health 
varies  in  different  individuals,  but  as  a  rule  the  left  is 
slightly  larger  than  the  right,  and  situated  somewhat 
higher  up.  The  former  is  semilunar  in  shape,  while 
the  latter  is  more  triangular,  and  somewhat  resembles 
a  "  cocked  hat." 

In  structure  these  glands  are  made  up  of  a  central 
portion,  or  medulla,  and  a  peripheral  part,  or  cortex. 
The  former  is  composed  of  highly  vascular  cells,  em- 
bedded in  a  venous  plexus,  which  secrete  adrenalin; 
owing  to  this  property  they  stain  more  or  less  deeply 
with  chromate  salts,  which  has  earned  for  them  the 
name  of  "  chromaffin  cells."  According  to  the  depth 
of  stain  which  the  cells  of  the  medulla  take,  the  degree 
of  activity  of  their  secretion  can  be  roughly  estimated. 

The  medulla  of  the  suprarenal  gland  has  very  close 
nervous  relations,  which,  from  a  morphological  stand- 
point, would   be  expected.     For  early  in  embryonic 


THE  ADEENAL  GLANDS  153 

life  neuroblastic  cells  emigrate,  and  while  some  settle 
in  front  of  the  spinal  cord,  forming  the  ganglia  of 
the  sympathetic  chain,  others  eventually  become  the 
visceral  ganglia;  while  another  group,  not  converted 
into  nerve  ganglia,  remain  in  close  connection  with  the 
k\iney,  forming  the  medullary  cells  of  the  adrenals, 
\*liich  secrete  its  active  principle.  As  well  as  the 
medulla,  which  is  formed  in  this  manner,  certain 
clumps  of  cells  stray  farther  afield,  forming  accessory 
bodies  external  to  the  main  gland. 

The  importance  of  these  facts  is  shown  by  two 
characteristics  of  the  gland ;  the  first  is  that  it  is  these 
cells,  originally  formed  from  the  same  embryological 
tissue  as  the  great  ganglia,  which  secrete  adrenalin; 
the  second  is  that  this  secretion  stimulates  only  that 
plain  muscle  in  the  body  which  is  supplied  by  the 
sympathetic  system.  That  this  is  so  can  be  verified 
by  electrical  stimulation  of  the  sympathetic  nerves, 
which  corresponds  exactly  with  the  result  of  adrenalin 
stimulation. 

The  exact  composition  of  adrenalin  has  been  dis- 
covered by  Takamine,  to  whom  we  owe  the  isolation 
of  this  substance;  and  he  shows  that  it  is  ortho-dioxy- 
phenyl-ethanol-methylamine.  Its  secretion  into  the 
blood-stream  is  controlled  by  the  splanchnic  sym- 
pathetic nerves.  Moreover,  the  amount  of  secretion 
has  been  shown  to  depend  largely  on  other  factors, 
both  mental  and  physical.  Thus,  mental  agitation — 
fright,  emotion,  hurried  exertion,  etc. — all  exert  an 
influence  upon  the  secretion  of  this  substance.    It  is 


154    THE  OEGANS  OF  INTEBNAL  SECRETION 

to  the  cells  of  the  medulla,  therefore,  that  we  owe 
this  important  hormone — in  this  case  a  true  hormone, 
as  it  is  an  excito -tonic  chemical.  These  cells,  it  must 
be  remembered,  have  an  extremely  intimate  connec- 
tion with  the  sympathetic  nervous  system;  this  is 
important,  as  we  shall  see  when  we  discuss  the  effects 
of  hypo-adrenia. 

The  other  part  of  the  gland  is  of  different  structure, 
and  is  composed  of  fatty  material;  a  doubly  refractive 
lipoid  is  found  in  the  cortex,  with  which  this  part  of 
the  gland  is  loaded.  The  cortex  is  very  much  larger 
than  the  medulla;  in  fact,  it  forms  about  90  per  cent, 
of  the  whole  gland. 

Included  in  the  chromaffin  system  are  the  following 
bodies:  the  medulla  of  the  suprarenal  gland,  the 
carotid  gland,  and  the  intercarotid  body,  the  accessory 
adrenals,  and  some  of  the  cells  of  the  anterior  lobe 
of  the  pituitary  body  which  give  the  same  reaction 
to  chromate  salts. 

While  the  medulla  is  in  reality  a  part  of  the  nervous 
system,  at  all  events  morphologically,  the  cortex  is 
not  in  any  way  connected  or  controlled  by  the  sym- 
pathetic nerves.  From  an  embryological  standpoint, 
its  cells  are  derived  from  the  same  neighbourhood 
as  the  sexual  glands,  and  as  the  testes  or  ovaries 
descend  they  carry  with  them  processes  from  the  same 
area.  Elliott  maintains  that  there  is  reason  to  believe 
that  some  buds  of  this  nature  are  embedded  in  the 
sex  gland  itself,  giving  rise  to  the  lutein  cells  of  the 
ovary  or  the  interstitial  cells  of  the  testis.1 


THE  ADRENAL  GLANDS  155 

The  cortical  cells,  however,  are  glandular  structures, 
and  appear  to  supply  some  secretion  which  influences 
the  growth  and  reproductive  powers  of  the  individual. 
This  has  been  demonstrated  clinically,  for  cases  are 
on  record  where  tumours  of  the  adrenal  cortex  have 
been  found  in  cases  where  the  characteristics  of  the 
opposite  sex  have  developed;  in  one  girl,  quoted  by 
Elliott,  the  menses  ceased,  a  beard  commenced  to 
grow,  and  the  body  took  on  masculine  characters. 

It  is  stated,  also,  that  enlargement  of  the  adrenal 
cortex  takes  place  during  breeding  and  pregnancy: 
and  feeding  of  young  animals  with  adrenal  gland 
substance  seems  to  stimulate  the  growth  of  the  testes.* 

An  interesting  case,  in  which  an  autopsy  was  per- 
formed, has  been  recorded. f  The  patient  was  a 
woman,  age  unstated,  who  was  bald,  but  had  a  dense 
beard  and  moustache.  There  had  been  amenorrhcea 
for  three  years,  and  there  was  pigmentation  of  the 
face.  At  the  post-mortem  examination,  the  right 
adrenal  gland  was  found  to  be  hypertrophied,  and 
weighed  141  grammes. 

Effects  o!  Removal  of  the  Adrenals. 

Since  the  time  of  Brown-Sequard  it  has  been  known 
that  removal  of  the  adrenals  was  followed  by  death, 
and  that  the  cause  of  death  was  the  loss  of  the  internal 
secretion  of  these  bodies.     That  death  is  not  due  to 

*  Vincent,  S.,  quoted  in  Endocrinology,  October-December , 
1917,  p.  516. 
t  Ibid.,  p.  534. 


156   THE  ORGANS  OF  INTERNAL  SECRETION 

shock  is  shown  by  the  fact  that  the  animal  shows  no 
symptoms  for  the  first  day  after  the  operation,  that 
in  many  animals  life  is  preserved  for  several  days,  and 
finally,  the  symptoms  which  precede  death  are  those 
now  known  to  be  due  to  loss  of  the  adrenal  secretion, 
and  are  not  those  due  to  shock. 

Removal  of  one  capsule  appears  to  have  no  dele- 
terious effect  upon  the  animal.  It  lives  quite  happily 
until  the  other  adrenal  is  removed,  when  death  occurs, 
usually  within  thirty-six  hours  (Sajous). 

To  understand  whether  the  suprarenal  capsules  are 
as  essential  to  life  in  man  as  in  the  lower  animals  it  is 
necessary  to  consider  the  effects  of  a  disease  which  robs 
the  blood  of  its  adrenal  content.  Many  difficulties 
stand  in  the  way  here,  for,  as  Sajous  says,  the  effects 
of  growth  of  the  adrenals  are  slow  in  their  manifesta- 
tions; other  viscera  may  be  involved  and  metastatic 
growths  may  be  present,  all  of  which  factors  make  the 
clinical  study  very  difficult.  The  one  condition  which 
is  able  to  help  us  in  studying  the  symptoms  of  a  sudden 
loss  of  adrenal  secretion  is  haemorrhage.  Sajous 
quotes  Francois  Arnaud's  eighty  cases  of  "  suprarenal 
apoplexy."  Briefly,  these  showed  either  sudden 
death  or  death  in  a  short  period,  the  autopsies  reveal- 
ing hemorrhagic  foci  either  into  both  capsules  or 
haemorrhage  into  one  capsule  and  congestion  of  the 
other.  Of  seventeen  cases  of  sudden  death,  fifteen 
showed  "  suprarenal  apoplexy  in  both  organs,  while 
two  showed  involvement  of  one  organ.  These  two 
instances  might  invalidate  the  evidence  adduced,  could 


THE  ADKENAL  GLANDS  157 

the  sudden  death  in  them  not  be  shown  to  have  been 
due  to  other  causes.  But  such  is  the  case;  in  the 
one  .  .  .  the  hemorrhagic  adrenal  had  been  ruptured, 
and  the  patient  died  of  haemorrhage  into  the  peritoneal 
cavity;  in  the  other  .  .  .  death  had  resulted  from 
uraemia,  due  to  granular  and  cystic  degeneration  of  the 
kidneys."* 

The  loss  of  one  adrenal  in  man  produces  results 
analogous  to  the  same  condition  in  animals,  as  is 
proved  by  the  operative  removal  of  growths  of  the 
suprarenal.  We  may  assume,  therefore,  that  in  man, 
as  in  animals,  the  loss  of  one  suprarenal  capsule  is 
followed  by  no  bad  result,  whereas  the  loss  of  both  is 
fatal. 

Functions  of  the  Adrenal  Bodies. 

The  first  point  to  emphasize  in  this  section  is  the 
far-reaching  and  important  part  which  the  internal 
secretion  of  the  adrenals  plays  in  promoting  the  bodily 
harmony.  This  will  be  easy  to  understand  when  we 
realize  that  these  glands  are  essential  to  life,  and  that 
their  removal  is  followed  by  an  early  death. 

It  has  been  shown  that  the  adrenal  secretion,  when 
injected,  has  a  marked  effect  in  raising  blood-pressure, 
and  that  the  injection  of  blood  from  the  suprarenal 
vein  into  a  normal  animal  has  a  similar  effect.  Ex- 
periments have  likewise  been  performed  to  show  that 
it   is  the  loss  of  the  blood-pressure-raising  substance 

*  Sajous,  "Internal  Secretions  and  Principles  of  Medicine,'* 
vol.  i.,  p.  7. 


158    THE  ORGANS  OF  INTERNAL  SECRETION 

after  removal  or  disease  of  the  adrenals  which  is 
responsible  for  the  symptoms;  for  the  injection  of  the 
adrenal  blood  will  remove  or  modify  these  symptoms, 
while  this  result  is  obtainable  with  no  other  extract — 
e.g.,  thyroid,  pancreas,  kidneys,  liver,  spleen,  etc.  We 
can  assume,  therefore,  that  the  adrenals  secrete  into 
the  adrenal  veins  a  substance  which  is  essential  to  life, 
This  substance  is  responsible  for  the  maintenance  of 
the  blood-pressure  and  for  the  stimulation  of  the 
cardiac  tone.  That  this  latter  effect  is  not  due  to 
stimulation  of  the  vagus  is  shown  by  experiments, 
notably  of  Biedl,  who  found  that  injection  of  supra- 
renal extract  raised  the  blood-pressure  even  when  the 
entire  spinal  cord  had  been  removed.  Its  action  upon 
the  muscular  wall  of  the  vascular  system — indeed,  upon 
the  muscular  system  in  general — is  of  a  constricting  or 
tonic  nature.  A  freshly  excised  vessel — one,  that  is, 
freed  from  all  nervous  control — responds  to  a  solution 
of  suprarenal  extract  (Oliver  and  Schafer,  quoted  by 
Sajous). 

Suprarenal  extract  has  been  shown  by  the  same 
investigators  to  act  directly  upon  the  muscles  of  the 
bloodvessels,  even  after  section  of  the  cord. 

The  absence  of  muscular  tone,  and  the  presence  of 
vaso- dilatation,  which  is  characteristic  of  hypo-adrenia, 
may  be  used  as  evidence  of  the  functions  of  the  supra- 
renal glands.  The  work  of  the  adrenal  secretion  is 
concerned,  inter  alia,  in  the  maintenance  of  the  vascular 
tone,  and  consequently  the  blood-pressure.  It  has  a 
direct  action  upon  the  heart  itself,  and  Biedl  shows 


THE  ADRENAL  GLANDS  159 

that  an  injection  of  suprarenal  extract  increases  both 
the  rapidity  and  power  of  the  cardiac  contractions. 
The  action  of  adrenalin  is  "  wholly  confined  to  tissues 
with  a  sympathetic  innervation;  and,  moreover  .  .  . 
the  effect  of  adrenalin,  in  any  part  of  the  body,  is 
identical  with  that  produced  by  electric  stimulus  of  the 
sympathetic  nerve  supplying  that  part.  Where  the 
influence  of  the  nerve  is  stimulating,  exciting  contrac- 
tion or  promoting  secretion,  the  action  of  adrenalin 
will  also  be  stimulating.  Where,  however,  irritation 
of  the  nerve  is  followed  by  inhibition,  the  injection  of 
adrenalin  will  also  produce  inhibition."*  We  will  now 
study  the  chemistry  of  the  adrenal  secretion  and  its 
effects  upon  the  body. 

Adrenalin. 

The  active  principle  wilich  is  secreted  by  these  glands 
has  been  named  "  adrenalin."  It  possesses  certain 
very  definite  characteristics,  and  is  a  necessary  secre- 
tion for  the  continuance  of  life,  for,  as  we  have  seen, 
loss  of  both  adrenals  is  fatal,  although  one  adrenal  can 
be  removed  without  any  apparent  ill  effects. 

With  regard  to  adrenalin  itself,  its  most  striking 
characteristic  is  its  power  of  raising  blood-pressure, 
even  when  injected  in  small  doses.  Experimentally, 
about  one-twentieth  of  a  milligramme  when  injected 
into  an  animal  is  sufficient  to  cause  a  considerable 
rise  in  the  sphygmomano metric  reading;  which,  again, 

*  Biedl,  "The  Internal  Secretory  Organs,"  p.  189. 


160   THE  ORGANS  OF  INTERNAL  SECRETION  . 

is  even  more  noticeable  if  the  vagus  is  put  out  of 
action,  as  this  substance  also  causes  a  slowing  of  the 
pulse  when  injected.  If  this  is  done,  the  blood- 
pressure  may  rise  in  quite  a  remarkable  manner. 
This  effect  is  produced  by  a  vaso-constricting  action 
upon  the  walls  of  the  peripheral  bloodvessels.  Oliver 
and  Schafer  showed,  by  means  of  oncometric  readings, 
that  the  volume  of  the  viscera  was  very  markedly 
reduced  by  adrenalin,  while  the  volume  in  the  ex- 
tremities was  increased  owing  to  the  excess  of  blood 
reaching  them  from  the  splanchnic  area. 

Adrenalin,  or  ortho  -  dioxyphenyl  -  ethanol  -  methyl- 
amine,  is  a  near  relation  of  ty rosin,  or  oxy phenyl- amino- 
propionic  acid,  one  of  the  products  of  the  decomposition 
of  proteids. 

A  full  account  of  the  chemistry  and  physiology  of 
adrenalin  will  be  found  in  Biedl's  book  on  the  internal 
secretory  organs,  in  Swale  Vincent's  book,  and  in 
many  other  studies  of  this  subject.  Sufficient  has 
now  been  said  to  show  that  this  secretion  is  very  im- 
portant in  bodily  metabolism,  and  exerts  a  considerable 
influence  upon  the  cardio -vascular  system.  The  cortex 
is  supposed  to  have  an  internal  secretory  function, 
which  is  concerned  in  neutralizing  the  poisonous 
products  of  muscular  activity.  In  other  words,  the 
medullary  secretion  exerts  an  angio -tonic  influence, 
while  the  cortical  is  concerned  with  neutralizing  toxins. 
There  seems  to  be  a  good  deal  of  evidence  that  the 
adrenal  secretion  is  in  some  way  concerned  with  mus- 
cular energy;  it  is  a  well-known  fact  that  in  Addison's 


THE  ADEENAL  GLANDS  161 

disease,  where  hypo-adrenia  exists,  muscular  asthenia 
is  a  marked  symptom;  also  that  muscular  power  is 
raised  "  after  adrenal  secretion  is  invoked,  or  after 
epinephrin  is  injected."2  Where  the  adrenal  glands 
are  injured  (which  sometimes  happens  during  operative 
procedures  in  the  neighbourhood  of  the  kidney)  or 
diseased,  there  can  be  little  doubt  that  muscular 
efficiency  is  diminished.  Langlois  has  shown  that  the 
adrenals  are  concerned  in  the  destruction  of  muscle 
poisons.3  So  we  are  justified  in  assuming  that  one 
function  of  the  secretion  of  these  glands  is  to  keep 
up  cardio-vascular  tone,  while  another  is  to  neutralize 
poisons  elaborated  during  muscular  energy. 

It  will  have  been  noticed  that  we  have  laid  stress 
here  upon  the  intimate  relation  between  the  adrenals 
and  the  sympathetic  system.  The  present  writer  has 
on  several  occasions  laid  stress  upon  the  sympathetic 
symptoms  so  commonly  present  in  neurasthenia,  and 
has  hazarded  a  theory  that  in  many  instances  of  this 
condition  the  underlying  cause  is  sympathetic  in- 
volvement.4 The  low  blood-pressure,  the  generalized 
asthenia,  the  vasomotor  symptoms,  are,  certainly  in 
the  majority  of  cases  of  true  neurasthenia,  the  most 
striking  features.* 

*  It  has  been  shown  that  an  intramuscular  injection  of 
1  milligramme  of  adrenalin  caused  an  increase  of  secretion  of 
hydrochloric  acid  in  the  stomach,  and  augmentation  and  accelera- 
tion of  the  contractions  of  the  gastro-intestinal  tract. 

The  fact  that  neurasthenia  is  so  often  associated  with  gastro- 
intestinal atony,  and  the  possibility  that  this  is  due  to  hypo- 
adrenalism  is  interesting. 

11 


162   THE  OEGANS  OF  INTEENAL  SECRETION 

Following  up  this  line  of  argument,  we  should 
expect  to  see  much  improvement  in  these  patients 
after  the  administration  of  a  vaso-tonic  hormone,  such 
as  adrenalin.  And  in  many  cases,  in  the  experience  of 
the  writer,  this  has  happened.  Doubtless  some  patients 
suffer  from  a  combined  endocrinous  derangement,  and 
these  would  not  of  necessity  benefit  from  adrenal 
administration  alone.  But,  nevertheless,  the  similarity 
between  hypo-adrenia  and  neurasthenia  is  sufficiently 
striking  to  be  noted. 

The  features  of  a  disorganization  of  the  adrenal 
system  are  daily  receiving  more  attention,  and  Sargent 
"  has  distinguished  three  different  types  of  adrenal  in- 
sufficiency— the  chronic,  the  subacute,  and  the  acute."6 
He  maintains  that  many  of  the  manifestations  of 
acute  illnesses  are  due  to  adrenal  insufficiency.  It  is 
obvious  that  such  features  might  conceivably  be  due 
to  this  cause,  and  when  further  light  has  been  shed 
upon  the  endocrine  glands,  it  is  probable  that  we  shall 
have  to  revise  many  of  our  existing  views  on  the 
manifestations  which  accompany  febrile  disturbances. 
We  shall  certainly  have  a  better  opportunity  of  ex- 
plaining factors  hitherto  regarded  as  necessary  but 
inexplicable  features  of  many  diseases. 

[Adrenal  Insufficiency. 

We  have  already  referred  to  the  views  held  by 
Sajous  on  the  adrenal  system,  and  the  importance  he 
ascribes  to  this  secretion  in  the  maintenance  of  efficient 


THE  ADKENAL  GLANDS  163 

oxidation.     His  views  upon  adrenal  insufficiency,  or 
hypo-adrenia,  may  be  summarized  as  follows: 

.  .  .  Hypo-adrenia,  or  insufficiency  of  the  adrenals, 
means  far  more  than  the  effects  of  lowered  blood- 
pressure  and  the  adequate  destruction  of  muscular 
wastes;  it  means,  besides,  inadequate  oxidation  and 
therefore  imperfect  tissue  metabolism  and  nutrition, 
and  also  impairment  of  the  autoprotective  functions 
of  the  body  at  large"*  The  three  clinical  forms  of  this 
disorder  Sajous  describes  as  functional  hypo-adrenia, 
where  the  adrenals  are  functioning  inadequately, 
although  not  the  seat  of  organic  disease;  progressive 
hypo-adrenia,  or  Addison's  disease,  where  the  activity 
of  the  adrenals  is  progressively  impaired  by  organic 
lesions;  and  terminal  hypo-adrenia,  occurring  as  a 
sequela  to  infectious  diseases  and  toxaemia. 

The  symptoms  can  be  studied  together.  Of  prime 
importance  is  a  low  blood-pressure,  an  asthenic  condi- 
tion of  mind  and  body,  a  subnormal  temperature,  a 
headache  of  a  "  vacuum  "  nature,  and  the  dermo- 
graphic  sign  described  by  Sargent,  f  The  same  observer 
refers  to  certain  complications  of  convalescence,  which 
he  regards  as  due  to  a  subacute  inflammation  of  the 
adrenals;  while  other  observers  also  lay  stress  upon  the 
exhaustion  which  may  supervene  during  the  course  of 
a  fever.  This  may  presumably  be  due  to  an  exhaus- 
tion of  the  adrenals,  produced  by  their  efforts  to  safe- 

*  "Internal  Secretions  and  Principles  of  Medicine,"  p.  82. 
|  This  consists  in  a  white  line  which  appears  on  the  skin  of 
the  abdomen  when  lightly  stroked  with  the  finger. 


164  THE  ORGANS  OF  INTERNAL  SECRETION 

guard  the  organism  from  toxaemia.6  It  is  quite 
possible  that  these  small  glands  play  an  important 
part  in  all  such  febrile  states,  in  neutralizing  toxins, 
and  in  helping  to  maintain  blood-pressure.  In  any 
case,  it  is  stated  that  their  administration  in  such  con- 
ditions can  be  relied  upon  to  counteract  these  effects. 

The  clinical  state  of  the  patient  with  Addison's 
disease  needs  no  detailed  description  here.  The 
flabby  atony  and  muscular  weakness,  the  vasomotor 
debility,  as  shown  in  the  coldness  of  the  skin  surface, 
as  well  as  the  characteristic  pigmentation,  are  too  well 
known  to  require  minute  detailing.  As  Elliott  points 
out,  all  the  symptoms,  except  the  pigmentation,  can 
be  explained  by  the  vasomotor  derangement  and  the 
paralysis  of  the  sympathetic  nerves.7 

There  is  also  in  this  disease  gas tro -intestinal  dis- 
turbance, as  shown  by  vomiting  and  diarrhoea;  but  the 
danger  undoubtedly  lies  in  the  risk  of  heart-failure. 
Other  symptoms  are  anorexia  with  deficient  appetite, 
sometimes  constipation,  attacks  of  vertigo,  syncopal 
attacks,  subnormal  temperature,  with  coldness  of  the 
extremities.  There  are  frequently  found  a  persistent 
thymus,  an  enlarged  spleen,  more  or  less  generalized 
hypertrophy  of  the  lymphoid  tissue  of  the  body,  par- 
ticularly of  the  stomach  and  intestines.  There  is 
usually  some  degree  of  wasting;  indeed,  in  the  more 
severe  cases  a  considerable  degree  of  emaciation  may 
be  present.  These  constitute  the  graver  form  of  the 
disease.  As  a  rule,  although  muscular  strength  is  very 
markedly  diminished,  general  nutrition  is  not  affected. 


THE  ADRENAL  GLANDS  165 

Death  occurs  from  asthenia,  delirium  or  convulsions, 
sudden  syncope,  or,  in  some  cases,  generalized  miliary 
tubercle.  The  main  features  of  Addison's  disease  are 
the  markedly  feeble  pulse,  the  extreme  asthenia,  the 
pigmentation,  and  the  gastro-intestinal  disturbance. 

The  milder  degrees  of  hypo-adrenia  are  those  to 
which  we  have  already  referred,  and  they  are  fre- 
quently labelled  "  neurasthenia."  That  is  to  say,  the 
main  features  are  asthenia,  vasomotor  disturbances, 
and  a  low  blood-pressure.  In  speaking  of  these  forms, 
Harrower  says:  "  The  disorders  of  the  adrenals,  accom- 
panied by  anatomic  changes,  are  fortunately  not  very 
common,  while  functional  hypo-adrenia  (sometimes 
termed  '  hypo-epinephrinia  '),  varying  very  greatly  in 
degree  and  the  consequent  manifestations,  is  of  fre- 
quent occurrence.  In  general,  the  evidence  of  the 
presence  of  such  conditions  is  lack  of  vascular  tone, 
hypotension,  myasthenia,  and  instability  of  the  sym- 
pathetic nervous  system.  This  class  of  disorders  is 
still  frequently  overlooked,  and,  because  of  the  intimate 
relations  of  the  endocrinous  organs,  almost  invariably 
associated  with,  and  complicated  by,  disturbances  in 
other  internal  secretory  organs."8 

It  might  be  expected  that  the  extreme  weakness  and 
asthenia  which  are  associated  with  this  condition 
would  be  accompanied  by  great  bodily  wasting.  But 
this  is  by  no  means  always  so;  in  fact,  the  bodily 
weight  usually  is  not  lost  in  any  marked  degree.  It 
may  be  that  this  is  due  to  an  increased  storage  of  fat 
or  carbohydrate  in  the  body,  due  to  the  diminished 


166   THE  ORGANS  OF  INTERNAL  SECRETION 

glycogenesis ;  for  we  know  that  an  injection  of  adrenalin 
increases  the  conversion  of  glycogen  into  glucose,  and 
may  produce  glycosuria;  therefore  a  diminished 
adrenalin  content  in  the  blood-stream  might  prevent 
a  utilization  of  the  stored-up  glycogen,  and  produce  a 
diminished  combustion.  This  would  be  probable, 
seeing  that  the  bodily  heat  is  lowered,  with  an  extreme 
degree  of  subjective  feelings  of  chilliness. 

Treatment. 

Having  now  very  briefly  reviewed  the  symptoms  of 
hypo-adreoia,  we  will  turn  to  the  study  of  the  thera- 
peutics of  the  adrenals.  Opinion  is  divided  as  to  the 
beneficial  effects  which  result  from  the  administration 
of  adrenalin  to  patients  suffering  from  gross  deficiency 
of  this  hormone — i.e.,  Addison's  disease.  Thus,  Elliott 
says:  "  Neither  with  animal  experiments  nor  in  man 
has  treatment  with  adrenalin  been  proved  to  be  of 
value  in  prolonging  life.  I  have  used  hypodermic  and 
intravenous  injections  of  adrenalin  without  obvious 
benefit.  Still,  the  substance  is  worth  a  trial."  On 
the  other  hand,  Harrower  says:  "Addison's  disease 
was  naturally  first  among  the  disorders  in  which  this 
form  of  treatment  was  tried;  and  while  the  results  have 
been  by  no  means  uniform,  numerous  cases  are  recorded 
by  such  men  as  Oliver,  Langlois,  Osier,  Robin,  and 
others,  in  which  the  general  condition  was  improved, 
pigmentation  was  diminished,  and  nutrition  was  bene- 
fited.    In   most    cases    the   results    were   temporary, 


THE  ADEENAL  GLANDS  167 

though  Beclere  obtained  a  complete  and  permanent 
cure  in  one  case.  He  credits  the  treatment  with 
causing  a  compensatory  hypertrophy  of  the  un- 
affected areas  of  adrenal  tissue."9 

Again,  it  has  been  suggested  that  in  some  cases  the 
causation  is  solely  referable  to  the  adrenal  glands, 
while  in  others  the  sympathetic  system  is  at  fault,  with 
or  without  adrenal  disturbance;  and  that  in  the  first 
class  of  case  benefit  is  to  be  expected  from  adrenal 
therapy,  while  in  the  second  we  cannot  and  do  not  see 
improvement  from  the  administration  of  the  hormone. 
As  it  is  generally  believed  that  80  per  cent,  of  the 
patients  who  suffer  from  this  disease  are  the  subjects 
of  tubercle,  the  general  antitubercular  treatment  should 
be  insisted  upon,  whatever  hormonic  treatment  they 
receive.  In  any  case,  the  dose  of  adrenal  substance 
would  have  to  be  large,  and  Harrower  says  that  as 
much  as  2  or  3  grains  of  desiccated  gland  substance 
should  be  given  three  times  a  day. 

We  must  believe,  therefore,  from  the  summation  of 
evidence,  that,  so  far  as  is  at  present  known,  the  ad- 
ministration of  adrenalin  has  not  been  the  success  in 
Addison's  disease  that  it  was  expected  to  be.  But  the 
explanation  probably  is  that,  if  the  larger  part  of  the 
gland  is  destroyed  by  tubercular  or  other  mischief, 
the  substitution  of  its  secretion  is  not  sufficient,  and 
the  disease  progresses  in  intensity;  or  that  the  prepara- 
tion employed  is  not  assimilated  in  an  active  form. 
It  has  been  stated  that  adrenalin,  when  given  by  the 
mouth,  is  not  destroyed  in  the  stomach  nor  by  the 


168  THE  OEGANS  OF  INTERNAL  SECRETION 

pancreatic  secretion,  but  that  the  liver  acts  adversely 
upon  it  by  depriving  it  of  some  of  its  efficacy.  It  has 
been  suggested  that  it  is  better  administered  by  the 
rectum,  where  it  can  be  readily  absorbed  and  carried 
directly  to  the  vena  cava.  With  regard  to  the  utiliza- 
tion of  adrenal  extracts  for  other  conditions,  it  has 
been  tried  and  recommended  for  a  variety  of  diseases. 
Thus,  it  has  been  administered  as  a  vaso- tonic  in 
cholera,  with,  according  to  the  particular  author, 
who  believes  that  this  disease  is  an  "  acute  hypo- 
adrenia  due  to  poisoning  of  the  adrenals  by  toxins  of 
the  cholera  spirillum,"  immediate  and  gratifying 
success.10 

It  has  likewise  been  utilized  in  the  vomiting  of 
pregnancy,  in  the  belief  that  the  adrenals  stand  between 
the  body  and  the  toxaemias  of  pregnancy  which  arise 
in  the  chorionic  villi.  Again,  in  the  condition  known 
as  "  cyclic  vomiting  "  it  has  been  tried  with  apparent 
success. 

It  will  be  seen  from  these  quotations  that,  so  far,  the 
diseases  mentioned  have  been  acute,  and  often  present 
no  known  etiology.  It  is,  therefore,  more  than  possible 
that  the  chromaffin  system  is  at  fault.  But  there  are 
encountered  other  conditions  of  a  more  chrome  nature 
which  appear  to  yield  to  adrenalin,  and  these  are  more 
particularly  seen  in  children.  Thus,  a  boy  or  girl  who 
developes  asthenia,  in  some  cases  after  an  acute  specific 
illness,  with  languor,  hypopiesis,  and  "  backwardness  " 
at  school,  is  possibly  suffering  from  hypo-adrenia. 
And  it  has  been  stated  that  administration  of  adrenal 


THE  ADEENAL  GLANDS  169 

extract  counteracts  this  condition,  renders  the  patient 
more  active,  and  banishes  the  indolence. 

Again,  after  acute  illnesses  in  adults,  where  asthenia 
and  delayed  convalescence  is  a  marked  feature,  the  ex- 
hibition of  adrenal  extract  should  deserve  consideration. 
It  is  not  improbable  that  a  disturbance  of  the  adrenal 
hormone  (which,  it  must  be  remembered,  is  a  hormone 
in  the  real  sense  of  the  word)  contributes  to  the  slow 
recuperation  and  hinders  recovery.  Therefore,  an 
extract  of  the  adrenals  seems  to  be  indicated.  Or, 
alternatively,  a  pluriglandular  preparation  should  be 
selected  if  it  is  considered,  on  all  the  evidence,  to  be 
desirable. 

Adrenalin,  or  an  adrenal  extract,  has  been  tried  in 
exophthalmic  goitre,  but,  so  far  as  the  present  writer's 
experience  is  concerned,  the  results  have  not  been 
encouraging,  and,  in  view  of  the  physiological  data  re- 
ferred to  in  Chapter  L,  this  can  scarcely  be  wondered  at. 

Blair  Bell  believes  that  osteomalacia  should  be 
treated  by  means  of  suprarenal  extract — not  neces- 
sarily because  this  extract  is  antagonistic  to  the 
ovarian  hormone,  but  because  he  believes  there  is 
often  suprarenal  inadequacy  in  this  disease.11  He 
thinks  that  the  secretions  of  the  adrenals  are  of  value 
during  pregnancy  in  "  assisting  the  absorption  and 
retention  of  lime."  In  this  connection  it  is  interesting 
to  note  that  certain  observers  have  experimented  upon 
the  action  of  adrenalin  upon  the  growth  of  bone,  and 
have  found  that  animals  from  whose  bones  rings  of 
tissue  have  been  removed,  if  subjected  to  the  ingestion 


170   THE  ORGANS  OF  INTERNAL  SECRETION 

of  this  extract,  heal  with  bony  union  much  more 
rapidly  than  the  control  animals  who  are  not  sub- 
jected to  the  action  of  this  drug.  It  would  seem, 
therefore,  that  adrenalin  exerts  a  helpful  influence 
upon  the  growth  of  osseous  tissue. 

Vernet  believes  that  vertigo  can  be  usefully  treated 
by  administering  adrenal  extract.  This  view  is  based 
upon  the  vasomotor  origin  of  this  complaint,  and  upon 
the  fact  that  it  is  commonly  seen  in  chlorotic  girls,  at 
the  menopause,  and  in  gouty  subjects.  He  gives  from 
five  to  twenty  drops  of  the  1 : 1,000  solution  twice  daily 
for  ten  days. 

Now  as  to  the  methods  of  administrating  the  adrenal 
preparations,  and  the  different  varieties  which  may  be 
utilized.  The  extract  of  the  gland  may  be  given  either 
separately  or  in  combination  with  other  hormones. 
Thus,  Houssay  recommends  the  combination  of 
adrenalin  and  hypophysin,  and  maintains  that  given 
together  a  smaller  dose  of  the  former  extract  is  required, 
which,  as  it  is  the  more  toxic  of  the  two,  is  a  decided 
advantage.  "  The  combination  may  be  used  success- 
fully in  fulminating  intoxications  associated  with  hypo- 
tension, in  tachycardia,  and  in  myocarditis  toxica, 
either  subcutaneously  or  by  the  mouth.  The  com- 
bination produces  a  greater  and  more  persistent  local 
ischaemia  than  adrenalin  alone.  The  adrenalin  neu- 
tralizes the  powerful  enterokinetic  action  of  hypo- 
physin, while  the  active  constituent  of  the  posterior 
lobe  of  the  hypophysis  counteracts  the  mydriatic  effect 
of   the  adrenal  extract."12    Swann   has    found   that 


THE  ADKENAL  GLANDS  171 

moderate  doses  of  a  1  in  1,000  solution  of  adrenalin 
administered  hypodermically  completely  cured,  in  two 
doses,  urticaria. 

The  extract  of  this  gland  may  be  given  either  as  a 
liquid  preparation  or  as  a  solid  extract.  Adrenalin  or 
adrenalin  chloride  may  be  administered  by  the  mouth, 
hypodermically,  or  intravenously  (the  latter  in  emer- 
gencies). The  first  of  these  methods  is  the  routine  for 
the  majority  of  cases — i.e.,  where  the  treatment  is 
required  in  small  doses,  probably  over  a  lengthy  period. 
Again,  where  it  is  to  be  utilized,  not  because  there  is 
definite  evidence  that  the  adrenal  substance  is  de- 
ficient, but  either  as  a  counteraction  to  other  hormones 
which  may  be  presumed  to  be  in  excess  or  simply  for 
its  therapeutic  action,  this  preparation  may  be  relied 
on.  Orally  it  may  be  given  in  doses  ranging  from  2  to 
3  minims  up  to  J  drachm.  The  dose  hypodermically 
should  be  about  half — that  is  to  say,  up  to  15  minims. 

This  extract  has  also  been  used  in  the  treatment  of 
asthma,  with  a  considerable  degree  of  success.  It  may 
be  given  hypodermically  or  locally  as  a  spray  or  douche 
to  the  nasal  mucous  membrane. 

Preparations  of  the  gland  are  also  made  in  the  form 
of  dry  extracts,  but  the  dose  appears  to  vary  with 
different  authors.  Thus,  it  is  sometimes  recommended 
in  doses  ranging  from  J  to  3  grains  (for  mild  hypo- 
adrenia),  and  it  is  possible  that  this  variance  is  to 
be  explained  by  the  fact  that  different  authorities  are 
referring  to  different  preparations.  Again,  some  manu- 
facturers supply  a  tablet  containing  the  extract  of 


172   THE  OEGANS  OF  INTEKNAL  SECRETION 

several  of  the  ductless  glands,  such  as  thyroid,  pitui- 
tary, and  adrenals.  If  it  is  desired  to  give  a  pluri- 
glandular preparation,  such  as  this,  it  is  important  to 
know  the  exact  dose  of  each  extract  which  the  tablet 
contains.  A  more  detailed  reference  to  the  various 
preparations  will  be  found  in  Chapter  XIII. 

We  may  mention  here  a  possible  method  of  counter- 
acting hyperadrenia.  The  patient  with  over-action  of 
the  adrenals  is  by  no  means  uncommonly  met  with, 
but  the  accurate  treatment  of  such  a  case  is  difficult. 
He  is  usually  thin,  nervous,  with  digestive  instability 
and  disturbed  sleep.  It  is  always  worth  while  to  treat 
such  a  patient  with  pancreatic  extracts,  as  the  antag- 
onism between  the  adrenals  and  the  pancreas  is  well 
proven.  It  may  be  assumed  that  such  extracts  will 
help  to  antagonize  the  excessive  secretion  from  the 
suprarenal  glands,  and  thus  assist  in  the  maintenance 
of  a  normal  balance. 

Finally  as  to  the  contra-indications  of  adrenal 
therapy.  It  will  be  quite  obvious,  from  what  has 
already  been  said,  that  hypertension  is  an  absolute 
contra-indication ;  also  that  it  should  never  be  admin- 
istered in  diabetes,  as  it  is  well  known  that  the  output 
of  sugar  is  increased  by  the  administration  of  adrenalin. 
While  its  value  in  the  treatment  of  tuberculosis  is 
great,  its  employment  in  patients  suffering  from  phthisis 
should  be  carefully  considered,  bearing  in  mind  the 
possibility  of  haemoptysis. 

Provided  that  it  is  given  under  the  careful  observa- 
tion of  a  medical  man,  who  can  observe  the  changes 


THE  ADEENAL  GLANDS  173 

which  accrue  as  the  treatment  progresses,  more  par- 
ticularly with  regard  to  the  vascular  tension  and 
pulse,  it  is  not  only  a  safe  remedy,  but  a  particularly 
successful  one.  We  shall  refer  in  a  subsequent  chapter 
to  the  important  points  in  pluriglandular  therapy,  and 
to  the  factors  which  decide  our  choice  between  the 
prescription  of  a  single  hormone  or  a  preparation  con- 
taining the  extracts  of  several  of  the  ductless  glands. 

References. 

1  Elliott,  Practitioner,  vol.  xciv.,  No.  1,  p.  126. 

2  Edit.  Jour.  Amer.  Assoc,  1913,  lxi.  123. 

3  Harrower,  Practical  Hornione-Therapj',  p.  263. 

4  Geikie  Cobb,  Neurasthenia  :  Its  Causes  and  Treatment, 
Practitioner,  August,  1915  ;  see  also  article  on  the  Diagnosis  of 
Neurasthenia  in  Practitioner,  April,  1913. 

5  Sargent,  quoted  in  Practical  Hormone-Therapy,  p.  266. 

6  Sajous,  Hypo-adrenia  as  a  Cause  of  Death  in  Infections, 
and  its  Treatment,  Mo.  Cyc.  and  Med.  Bull.,  1911,  iv.  725. 

7  Elliott,  loc.  cit.,  pp.  127,  128. 

8  Harrower,  loc.  cit.,  p.  265. 

9  Harrower,  loc.  cit.,  p.  264. 

10  Harrower,  loc.  cit.,  quoted  from  Naame,  Jour,  de  Pract., 
1912,  xxiv.  87. 

11  Blair  Bell,  The  Internal  Secretions  and  Female  Charac- 
teristics, Proc.  Roy.  Soc.  Med.,  1913,  vi.  74. 

12  Quoted  in  Harrower's  book,  pp.  275,  276. 


CHAPTER  VIII 

THE   PANCREAS 

The  next  gland  which  we  must  study  in  connection 
with  the  endocrine  glands  is  the  pancreas.  And  from 
its  importance  in  the  bodily  metabolism,  an  importance 
which  is  receiving  fresh  proofs  every  day,  it  deserves  a 
high  place  in  any  volume  which  deals  with  the  internal 
secretions.  Apart  from  the  vital  nature  of  its  external 
secretion — that  is  to  say,  its  digestive  ferments — there 
is  an  ever-accumulating  mass  of  evidence  to  show 
that  the  pancreas  is  concerned  with  the  regulation  of 
carbohydrate  metabolism  in  an  even  more  important 
relation  than  are  the  thyroid  and  pituitary  glands. 

For  this  reason  alone,  therefore,  it  behoves  us  to 
have  a  practical  knowledge  of  the  pancreas  and  its 
functions,  and  to  familiarize  ourselves  with  the  results 
of  recent  physiological  research.  We  shall  therefore 
devote  this  chapter  to  a  consideration  of  the  structure, 
functions,  and  pathology  of  disorders,  of  this  gland, 
and  conclude  by  outlining  the  therapeutic  possibilities. 

Anatomy  and  Physiology  o!  the  Pancreas. 

The  pancreas  is  a  tubulo-racemose  gland,  situated 
transversely  across  the  posterior  wall  of  the  abdomen, 

174 


THE  PANCREAS  175 

at  the  back  part  of  the  epigastric  and  left  hypo- 
chondriac regions.  In  structure  it  resembles  the 
salivary  glands,  although  it  is  of  softer  consistency 
and  less  compact  than  these  organs.  It  is  composed 
of  a  head,  a  neck,  a  body,  and  a  tail;  while  its  duct 
has  received  the  name  of  "  the  canal  of  Wirsung." 
This  duct  opens  into  the  duodenum,  either  in  common 
with  the  ductus  communis  choledochus  or  else  by  an 
independent  orifice. 

The  gland  is  composed  of  alveoli,  loosely  held  to- 
gether by  connective  tissue,  containing  in  its  meshes 
cells  known  as  the  "islets  of  Langerhans."  These 
cells  are  of  great  importance,  for,  as  we  shall  see  later, 
they  are  concerned,  as  physiological  research  has 
shown,  in  the  production  of  a  hormone  which  governs 
carbohydrate  metabolism.  They  are  plentifully  sup- 
plied with  bloodvessels,  arranged  in  the  form  of  a 
compact  network  of  capillary  vessels. 

For  many  years  these  cells  have  been  known  to  exist, 
but  until  recently  their  function  has  been  hidden. 
Now,  however,  it  is  becoming  increasingly  clear  that 
they,  in  all  probability,  secrete  a  hormone  which  is 
absolutely  necessary  for  the  continuance  of  life.  Pre- 
vious to  the  recent  work  on  internal  secretion,  the  role 
played  by  the  pancreas  was  supposed  to  be  solely  one 
of  digestion ;  but  Bayliss  and  Starling  showed  as  long 
ago  as  1902  that  the  digestive  juices  of  the  pancreas 
were  capable  of  being  stimulated  by  a  substance 
known  a3  secretin,  which  is  derived  from  pro-secretin 
by   treatment   with   an   acid.     In   normal    digestion, 


176   THE  OEGANS  OF  INTERNAL  SECRETION 

prosecretin,  when  it  comes  into  contact  with  the  acid 
of  the  gastric  juices,  is  converted  into  secretin,  which 
sets  up  pancreatic  activity. 

The  external  secretion  of  the  pancreas  is  composed 
(according  to  Halliburton)  of  water,  organic  solids, 
and  inorganic  salts.  The  organic  solids  consist  of  the 
ferments  trypsin,  amylopsin,  steapsin,  and  a  milk- 
curdling  ferment,  together  with  other  less  important 
constituents,  such  as  traces  of  leucine,  tyrosine,  and  a 
small  amount  of  proteid  matter.1 

These  ferments  are  most  important  in  carrying  on 
the  digestive  processes  inaugurated  in  the  mouth  and 
stomach;  but  as  their  chemical  actions  are  physiological 
facts  not  directly  connected  with  our  study,  we  will 
not  deal  at  any  length  with  them  here.  What  does 
concern  us  in  this  connection  is  the  internal  secretion 
of  the  pancreas,  and  the  influence  it  exerts  upon  meta- 
bolism in  general. 

As  we  have  already  said,  the  islets  of  Langerhans 
are  of  great  interest  in  studying  the  internal  secretion 
of  this  gland,  as  recent  work  has  confirmed  the  theory 
that  it  is  this  part  of  the  pancreas  which  is  so  essential 
to  life. 

The  Internal  Secretion  of  the  Pancreas. 

In  1889,  V.  Mering  and  Minkowski  made  the  impor- 
tant discovery  that  removal  of  the  whole  or  of  a  large 
part  of  the  pancreas  was  followed  by  hyperglycemia, 
and  eventually  fatal  diabetes.  That  this  is  not  due 
to  the  abolition  of  the  external  secretion  is  proved  by 


THE  PANCREAS  177 

the  discovery  that,  if  pancreatic  substance  is  grafted 
into  an  animal,  glycosuria  is  prevented,  although  the 
secretion  of  ferments  into  the  alimentary  canal  is 
absent.  Again,  if  the  pancreatic  duct  be  tied,  the 
pancreatic  tissue  atrophies,  but  it  is  believed  that  the 
islets  of  Langerhans  remain  in  a  sufficiently  normal 
condition  to  furnish  the  body  with  the  internal  secre- 
tion. For  although  diabetic  symptoms  do  not  ensue 
after  ligature  of  the  duct  (in  spite  of  the  atrophy  of 
the  pancreas),  if  the  organ  be  subsequently  removed 
glycosuria  results. 

Again,  in  support  of  the  belief  that  the  islets  are 
responsible  for  an  internal  secretion,  it  has  been  noted 
that  these  cells  are  degenerated  in  some  cases  of  dia- 
betes, which  is  strong  presumptive  evidence  that  pan- 
creatic diabetes  owes  its  origin  to  an  interference  with 
an  internal  secretion  provided  normally  by  the  cells 
in  the  islets  of  Langerhans.  Schafer  says  that  these 
cells  have  a  common  origin  with  the  cells  of  the  duct, 
although  they  are  not  connected  with  the  alveoli  or 
ducts.2 

Without  going  into  elaborate  details  of  pancreatic 
physiology,  we  must  give  the  bare  outline  of  the  struc- 
ture and  behaviour  of  this  gland,  in  order  that  its 
bearing  on  the  hormone  balance  and  its  relation  to 
carbohydrate  metabolism  may  be  clear. 

To  summarize  the  modern  view  as  to  the  relationship 
which  the  pancreas  bears  to  diabetes,  we  may  say  that 
it  may  fairly  be  assumed  that  the  islets  of  Langerhans 
secrete  a  substance  which,  circulating  in  the  blood- 

12 


178   THE  ORGANS  OF  INTERNAL  SECRETION 

stream,  prevents  an  undue  amount  of  glucose  from 
accumulating  in  this  fluid.  Hedon  has  shown,  by- 
passing the  blood  of  normal  animals  through  a  de- 
pan  creatized  dog,  that  glycosuria  may  be  prevented. 
This  serves  to  show  that  the  blood  of  normal  animals 
contains  some  substance  or  substances  which  regulate 
carbohydrate  metabolism. 


The  Relation  of  the  Pancreas  to  Diabetes. 

This  evidence,  when  added  to  the  facts  about  the 
islets  to  which  we  have  already  referred,  is  sufficiently 
convincing  to  warrant  us  in  assuming  that  the  pancreas 
possesses  an  internal  secretion  which,  by  its  presence 
in  the  blood,  regulates  sugar  storage,  although  its  in- 
fluence upon  the  gly oogenetic  properties  of  the  liver 
has  still  to  be  determined.  In  this  connection,  Schafer 
suggests  that  "  the  substance  produced  by  the  pan- 
creas islets  may  be  a  chalonic  autacoid  which  tends  to 
inhibit  the  formation  of  glucose  from  glycogen,  and 
incidently  to  promote  the  storage  of  glycogen,  so  that 
in  its  absence  the  glycogen  which  is  present  in  the 
liver  is  rapidly  converted  into  glucose,  and  the  sugar 
absorbed  from  the  alimentary  canal  formed  in  the 
body  is  not  stored  by  the  liver.  The  result  again 
will  be  hyperglycemia  and  glycosuria."3  Schafer 
proceeds  to  say  that  the  "hypothesis  that  there 
exists  a  chalonic  or  inhibitory  agent  in  the  internal 
secretion  of  the  pancreas  which  affects  carbohydrate 
metabolism  is  probably  the  correct  one."4 


THE  PANCREAS  179 

In  any  case,  the  evidence  as  to  the  part  played  by 
the  islets  of  Langerhans  in  the  production  of  diabetes 
is  very  complete;  the  discovery  by  Opie  that  a  man 
who  had  died  of  diabetes  possessed  atrophy  of  these 
cells  was  a  strong  confirmation  of  the  theory  that  these 
islets  possessed  some  such  function.  This  has  been 
confirmed  by  numerous  autopsies,  so  that  one  of  the 
greatest  authorities  on  this  subject,  Professor  Van 
Noorden,  now  maintains  that  no  diabetes  can  exist 
without  disease  of  Langerhans'  islands.5  This  author 
in  the  same  place  divides  diseases  of  the  islands  into 
two  groups:  those  which  result  from  diseases  of  their 
environment,  and  those  resulting  from  specific  disease 
of  the  islands  independent  of  their  surrounding  tissues. 
The  first  of  these  groups  would  include  such  affections 
as  inflammatory  conditions  of  metastatic  origin,  or 
inflammation  proceeding  up  Wirsung's  duct,  and  pan- 
creatic arteritis;  while  the  second  group  includes  "  con- 
genital constitutional  atony  of  the  island  system  " 
and  "  acquired  atony  of  the  same  system."  In  asso- 
ciation with  this  classification — that  is  to  say,  in 
support  of  the  idea  that  some  cases  of  diabetes  owe 
their  origin  to  disturbances  from  without  the  pancreas 
— Morris  believes  that  a  bacterial  infection  from  the 
duodenum  may  cause  pressure  upon  the  islets,  and 
thus  set  up  a  pancreatitis.  When  the  pancreatitis  is 
relieved,  the  pressure  disappears  and  likewise  the 
glycosuria.6 

The  present  writer  has  quoted  these  views  for  the 
reason  that  they  offer  a  feasible  theory  as  to  the  pro- 


180   THE  ORGANS  OF  INTERNAL  SECRETION 

duction  of  pancreatic  diabetes  in  man,  and  give  some 
idea  as  to  the  manner  in  which  interference  with 
Langerhans'  islets  may  be  brought  about. 

Apart  from  the  interest  of  the  recent  discoveries 
which  physiologists  have  made  about  the  functions  of 
the  pancreas,  these  discoveries  throw  an  added  light 
upon  the  part  which  this  gland  plays  in  the  general 
bodily  metabolism,  as  well  as  its  importance  in  support- 
ing the  hormomc  balance.  Again,  our  newly  found 
knowledge  explains  many  facts  which  were  hitherto 
known  as  facts,  but  lacked  an  explanation.  As  an 
example  of  this  assertion,  we  may  mention  one  factor 
which  characterizes  glycosuria — namely,  the  increased 
liability  to  infection.  It  has  been  known  for  many 
years  that  the  diabetic  possesses  little  phagocytic 
power,  and  that  he  is  not  only  a  bad  subject  for  opera- 
tion, but  also  extremely  prone  to  develope  concurrent 
diseases,  such  as  tubercle.  Many  observers  have 
drawn  attention  to  this  fact,  and  have  emphasized 
the  lowered  resistance  to  the  tubercle  bacillus  which 
diabetics  possess. 

H.  R.  Harrower  published  an  article  in  the  Practi- 
tioner, in  which  he  dealt  very  fully  with  the  influence 
of  the  pancreas  and  its  extracts  upon  infection;  and  he 
maintained  that  this  gland  is  concerned  with  defending 
the  body  against  bacterial  infection.  This  is  reprinted 
with  additions  in  his  recent  book,7  and  the  reader  is 
referred  to  this  chapter  for  an  able  and  comprehensive 
account  of  this  action  of  the  pancreas. 

In  discussing  the  action  of  the  pancreatic  hormone, 


THE  PANCBEAS  181 

we  must  bear  in  mind  that  it,  like  all  other  internal 
secretions,  has  a  relation  to  its  fellow-hormones,  and 
that  some  facts  bearing  upon  this  have  been  recently 
brought  to  light.  Thus,  it  has  been  shown  that  the 
thyroid  as  well  as  the  parathyroids  influence  pan- 
creatic activity,  but  in  opposite  relations.  The  thyroid 
appears  to  be  antagonistic  to  the  pancreatic  secretion, 
for  its  removal  tends  to  prevent  pancreatic  diabetes;* 
while  the  removal  of  the  parathyroids  assists  hyper- 
glycemia. We  have  already  seen  that  there  is  an 
increased  tendency  to  glycosuria  in  Graves'  disease, 
while  there  is  always  an  increased  sugar  tolerance  in 
the  opposite  condition,  submyxcedema. 

Another  factor  which  must  be  mentioned  when  dis- 
cussing sugar  metabolism  is  the  permeability  of  the 
renal  filter — that  is  to  say,  the  amount  which  the 
kidney  is  capable  of  passing  through  its  meshes.  The 
normal  sugar  content  of  the  blood  is  about  0-1  per 
cent.,  and  to  this  amount  the  renal  apparatus  is 
impermeable.  But  if  the  amount  exceeds  this  figure 
the  kidney  is  unable  to  resist  the  hyperglycemia,  and 
sugar  passes  into  the  urine.  A  marked  degree  of 
hyperglycemia  is  always  present  as  the  result  of 
extirpation  of  the  pancreas,  and  this  is  the  immediate 
cause  of  the  glycosuria.  The  immediate  production 
of  sugar  in  the  blood  in  excessive  quantities  following 
upon  removal  of  the  pancreas  is  doubtless  concerned 
with  several  facts  which  bear  upon  the  hyperglycemia. 
The  glycogen  in  the  liver  is  one  of  the  first  substances 

*  But  see  Chapter  L,  p.  29,  for  Gley's  views  on  this  subject. 


182   THE  OBGANS  OF  INTEENAL  SECRETION 

to  be  altered  by  the  operation,  and  this  is  very  markedly 
reduced  shortly  after  the  removal  of  the  gland.  After 
generous  feeding  with  carbohydrates,  moreover,  only 
traces  of  glycogen  are  able  to  be  discovered.  In 
contrast  to  this,  the  leucocytes  exhibit  a  very  high 
glycogen  content.  It  is  possible  that  this  freeing  of 
the  glycogen  reserves  is  one  source  of  the  increased 
amount  of  sugar  in  the  blood,  but  it  can  hardly  be 
the  only  one,  for  it  would  soon  be  exhausted.  The 
additional  sugar  must  come  from  albuminoids  and 
fats,  and  this  would  in  some  measure  account  for  the 
extreme  wasting  which  these  cases  show. 

So  much  for  a  few  facts  bearing  upon  the  relation 
between  the  pancreas  and  the  symptoms  of  diabetes. 
Now  we  will  discuss  a  little  more  fully  the  internal 
secretion  of  this  gland  before  turning  to  the  therapeutic 
consideration  of  the  pancreas. 

Origin  of  the  Pancreatic  Internal  Secretion. 

It  was  at  first  supposed  that,  if  an  internal  secretion 
existed  at  all  in  this  gland,  it  was  formed  by  the  same 
cells  which  manufactured  the  ferments — in  fact,  that 
such  cells  performed  a  double  action.  In  1869  Lan- 
gerhans  first  drew  attention  to  those  groups  of  cells 
which  have  since  borne  his  name,  and  from  their 
characteristics  it  is  now  assumed  that  they  are  re- 
sponsible for  the  internal  secretion.  They  are  com- 
posed of  badly  denned  polygonal  cells,  with  large 
nuclei,  and  a  very  free  blood-supply  which  comes  from 


THE  PANCEEAS  183 

capillar  bloodvessels  in  intimate  relation  to  the  cells. 
It  is  generally  believed  that  these  cells  have  no  com- 
munication with  the  acini  of  the  gland,  but  the  question 
is  not  definitely  settled.  In  some  of  the  lower  animals 
proof  is  forthcoming  that  there  exists  some  connection 
between  the  excretory  ducts  and  the  cells  of  the 
islands.*  Again,  it  is  believed  by  some  workers  that 
the  islets  play  a  part  in  the  production  of  the  external 
pancreatic  ferments,  or,  again,  that  the  islets  and  the 
acini  are  not  functionally  differentiated. 

The  action  of  adrenalin  upon  pancreatic  activity  is 
of  interest,  for  it  is  well  known  that  adrenalin  when 
injected  into  the  blood-stream  sets  up  a  temporary 
glycosuria;  but  it  is  not  equally  well  known  that  some 
observers  have  found  that  the  administration  of 
adrenalin  to  animals  has  been  followed  by  the  appear- 
ance of  necrosed  areas  in  the  islets  of  Langerhans. 
Although  the  action  of  adrenalin  in  producing  glyco- 
suria is  apparently  mainly  through  the  pancreas,  that 
this  is  not  solely  so  is  evidenced  by  the  fact  that  there 
is  an  increase  of  sugar  even  in  depancreatized  animals 
after  the  administration  of  adrenalin.  Again,  hyper- 
glycemia can  be  produced  by  means  other  than  dis- 
order of  the  pancreatic  functions  and  the  administra- 
tion of  adrenalin,  such  as  puncture  of  the  fourth 
ventricle  and  stimulation  of  the  splanchnics. 

A  fact   which  is  interesting  from  the   promise   of 

*  Some  observers  have  been  able  to  inject  the  islands  through 
the  ducts,  while  others  have  observed  connections  between 
lumina  in  the  islands  and  the  acini. 


184  THE  ORGANS  OF  INTERNAL  SECRETION 

therapeutic  possibilities  in  the  future  is  that  elicited 
by  Zuelzer — namely,  that  adrenalin  glycosuria  can  be 
overcome  by  the  administration  of  pancreatic  extracts 
and  juices;  for,  whether  due  to  an  antagonistic  action 
on  the  adrenal  hormone  or  to  its  effects  on  the  per- 
meability of  the  kidney,  it  shows  promise  of  further 
therapeutic  developments. 

It  has  been  stated  that  adrenalin  instilled  into  the 
eye  of  a  depancreatized  animal  causes  dilatation  of  the 
pupil,  which  does  not  occur  in  the  normal  animal,  and 
this  test  has  been  made  use  of  for  the  diagnosis  of  pan- 
creatic diabetes,  as  it  has  been  shown  that  it  is  like- 
wise present  in  man  in  some  cases  of  diabetes.  In  any 
case,  it  seems  that  it  will  not  be  long  before  further 
light  will  be  thrown  both  upon  the  relation  of  the  pan- 
creas to  the  production  of  diabetes,  and  also  upon  the 
site  of  production  and  the  more  exaot  nature  of  the 
internal  secretion. 

Therapeutic  Considerations. 

We  now  come  to  a  brief  consideration  of  the  thera- 
peutic possibilities  of  extracts  of  pancreas.  It  has 
been  necessary  in  this  chapter  to  deal  somewhat  fully 
with  diabetes,  as  the  study  of  this  condition  is  directly 
related  to  any  consideration  of  the  internal  secretion 
of  the  pancreas;  and  our  knowledge  at  the  present  time 
has  been  mainly  gained  by  experiments  in  the  pro- 
duction of  hyperglycemia  and  glycosuria  and  their 
relation  to  the  pancreas. 


THE  PANCREAS  185 

In  dealing  with  the  therapeutic  side  of  the  pancreas, 
we  must  realize  that  a  good  deal  of  difference  of  opinion 
exists  as  to  the  efficacy  or  otherwise  of  this  particular 
form  of  hormone-therapy.  First,  with  regard  to  the 
administration  of  pancreatic  extracts  in  cases  of 
diabetes,  Schafer,  writing  doubtless  from  the  experi- 
mental standpoint,  says:  "It  is  not  found  that  pan- 
creas extracts  have  the  effect  of  antagonizing  the 
results  of  pancreas  extirpation;  in  this  respect  they 
offer  a  parallel  to  the  negative  results  of  suprarenal 
extracts  in  antagonizing  the  effects  of  adrenal  depriva- 
tion."8 

It  must  be  remembered  that  it  is  not  maintained 
that  all  cases  of  diabetes  which  are  encountered 
clinically  are  of  necessity  due  to  pancreatic  disorders, 
in  spite  of  the  opinion  of  Van  Xoorden,  which  we  have 
already  quoted.  It  is  therefore  only  reasonable  to 
assume  that  some  cases  of  diabetes  which  we  treat 
with  pancreatic  extracts  may  be  due  to  causes  other 
than  pancreatic.  If  this  is  so,  we  must  not  expect 
to  improve  every  patient  suffering  from  glycosuria 
who  comes  under  our  care  by  the  administration  of 
pancreatic  preparations. 

The  reasons  why  we  may  expect  that  this  treatment 
will  not  be  universally  successful  are  summarized  by 
Harrower  as  follows: 

"  First,  not  in  every  case  of  diabetes  is  the  pan- 
creatic factor  present  or  prominent.  Second,  very 
few  preparations  of  pancreas  are  made  with  the  object 
of  specifically  supplying  as  much  as  possible  of  the 


186   THE  OEGANS  OF  INTERNAL  SECRETION 

islet  substance.  Third,  it  is  no  easy  matter  to  supply 
the  lacking  hormone,  for  it  is  normally  supplied  con- 
tinuously to  the  blood,  and  we  have  no  means  of  know- 
ing how  much  is  elaborated,  or,  in  disease,  how  much 
is  lacking,  in  each  case.  Fourth,  the  antagonism  of 
the  chromaffin  hormone  must  be  considered;  for  the 
diabetes  may  be  due  not  simply  to  a  deficiency  of 
the  pancreatic  internal  secretion,  but  to  an  exagger- 
ation of  that  of  the  adrenals  or  a  combination  of 
both.  Fifth,  evidently  several  other  factors  are 
concerned,  and  hence  the  hormone  treatment  of 
diabetes  alone  cannot  be  instituted  with  hopes  of 
success."9 

Having  given  the  reasons  why  this  method  of  treat- 
ing diabetes  is  at  present  not  entirely  successful,  we 
may  perhaps  be  allowed  to  quote  a  few  opinions  which 
are  favourable  to  pancreas-therapy.  Thus,  the  same 
author  a  little  farther  on  in  the  same  chapter  says: 
"  It  is  evident  that  the  pancreas  ferment  preparations 
may  have  an  excellent  influence  upon  glycosuria."10 
Harrower  explains  this  thus:  "This  is  probably  due 
to  the  restorative  action  on  the  pancreas  caused  by 
the  reinforcement  of  digestion,  and  the  removal,  in 
part  or  altogether,  of  the  pancreatic  disability,  which 
is  not  alone  reflected  upon  its  external,  but  also  on 
its  internal  secretion." 

Again,  Harrower  refers  to  trypsogen  (a  combination 
of  the  ferments  trypsin  and  amylopsin  with  the  internal 
secretion)  as  having  benefited  several  cases  of  un- 
doubted diabetes  mellitus;  occasionally  the  sugar  has 


THE  PANCREAS  187 

quite  disappeared,  more  often  the  symptoms  charac- 
teristic of  this  complaint  have  been  much  benefited, 
weight  has  been  increased,  polyuria  quite  controlled, 
and  sugar  reduced."11 

There  are  also  on  the  market  other  preparations  of 
pancreas,  some  of  which  are  composed  of  one  or  more 
of  the  pancreatic  ferments,  while  others  are  extracts 
of  the  whole  gland.  Before  proceeding  farther  with 
the  discussion  of  this  form  of  therapy,  we  must  em- 
phasize that  it  is  absolutely  essential  it  should  be  re- 
garded, in  so  far  as  diabetes  is  concerned,  as  an  adjunct 
rather  than  as  a  sole  form  of  treatment.  For  it  is 
quite  agreed  that  where  there  is  excessive  glycaemia 
there  is  every  reason  to  relieve  materially  the  strain 
upon  the  pancreas  by  limiting  the  ingestion  of  carbo- 
hydrates. Therefore,  so  far  as  this  disease  is  con- 
cerned, diet  should  always  be  the  primary  con- 
sideration, and  an  endeavour  to  replace  a  lost  or 
diminished  internal  secretion  a  justifiable  secondary 
one. 

Another  preparation  which  contains  the  extracts  of 
liver  and  pancreas  is  Kinazyme,  and  it  is  recom- 
mended by  its  manufacturers  to  increase  weight;  it  is 
also  said  to  be  a  valuable  adjunct  to  the  treatment 
of  tuberculosis.  It  may  be  presumed  that  this  not 
only  is  believed  to  encourage  normal  digestive  pro- 
cesses, but  also  to  raise  the  bodily  resistance  to 
infection. 

It  has  also  been  stated  that  extracts  of  pancreas  are 
useful  in  hypertension,  presumably  for  their  counter- 


188   THE  OBGANS  OF  INTERNAL  SECRETION 

acting  power  on  the  chromaffin  system.  In  cases 
where  there  is  some  evidence  of  hyperadrenia,  such 
treatment  should  be  given  a  trial.* 

Finally,  while  insisting  with  as  much  stress  as 
formerly  upon  dietetic  and  hygienic  principles  in  the 
treatment  of  diabetic  and  kindred  disorders,  the  prac- 
titioner should  bear  in  mind  preparations  of  this  gland ; 
for  it  is  quite  possible  that  such  preparations  will  turn 
the  scale  in  favour  of  the  patient,  while  if  left  solely 
to  the  conservative  method  of  withholding  carbo- 
hydrate food  it  might  turn  in  favour  of  the  disease. 
Such  therapy  as  is  offered  by  extracts  of  the  pancreas 
is  rational  and  harmless,  and  it  must  be  confessed  that 
there  is  an  opening  for  any  form  of  treatment  which 
will  make  the  lot  of  the  diabetic  an  easier  one.  For 
this  reason  alone,  even  if  no  other  is  forthcoming,  it 
is  advisable  to  try  this  form  of  opo-therapy  in  those 
diseases  where  it  may  be  assumed  that  the  pancreas 
is  at  fault;  not  only  in  definite  diabetes,  but  in  deficient 
digestion  (the  so-called  carbohydrate  dyspepsia),  either 
alone  or  combined  with  preparations  of  the  intestinal 
secretions,  to  which  the  pancreatic  ferments  have  so 
close  a  relation. 

*  For  further  details  of  hyperadrenalisru  see  Chapter  XII., 
p.  244. 

As  opposed  to  this  theory,  some  recent  experiments  on  the 
relation  between  the  pancreas  and  the  adrenals  state  that  the 
blood  in  the  suprarenal  veins  contains  less  adrenalin  after 
pancreatectomy  than  before,  which  may  indicate  that  the  func- 
tional loss  of  the  secretion  of  the  latter  gland  depresses  the 
action  of  the  former  (Endocrinology,  pp.  488-489). 


THE  PANCREAS  189 

These  diseases,  whose  name  is  legion,  offer  a  legi- 
timate scope  for  the  rational  practice  of  organo-therapy, 
and  so  far  as  assimilation  is  concerned  the  pancreas 
may  be  regarded  as  the  foundation,  which,  if  upset, 
even  by  temporary  or  slight  disturbances,  is  capable 
of  upsetting  the  balance  without  which  normal  meta- 
bolism is  impossible. 

References. 

1  Halliburton,  Handbook  of  Physiology,  p.  491. 

2  Schafer,  The  Endocrinic  Glands,  p.  125. 

3  Ibid.,  p.  129. 

4  Ibid.,  p.  130. 

5  Van  Noorden,  Practitioner,  vol.  xciv.,  Xo.  2,  p.  237. 

6  Morris,  Jour.  Am.  Med.  Assoc,  lx.,  1913. 

7  H.  R.  Harrower,  Practical  Hormone -Therapy,  ch.  vii 

8  Schafer,  loc.  cit.,  p.  128. 

9  Harrower,  loc.  cit.,  p.  104. 

10  Harrower,  loc.  cit.,  p.  106. 

11  Harrower,  loc.  cit.,  p.  107. 


CHAPTER  IX 

THE  SEXUAL  ORGANS  AND  THEIR  INTERNAL 
SECRETIONS 

It  will  only  be  possible  to  review  briefly  the  main 
features  of  the  sexual  organs  and  their  hormones.  For 
the  subject  is  so  vast,  and  the  difference  of  opinion 
which  exists  about  many  of  these  organs  and  their 
secretions  is  so  great,  that  it  would  necessitate  a  far 
too  lengthy  study  here.  We  shall  therefore  enumerate 
the  main  facts  with  regard  to  the  hormones  elaborated 
by  these  glands,  and  deal  briefly  with  the  relations 
between  these  secretions  and  those  of  other  of  the 
endocrine  glands. 

For  this  reason,  if  some  of  the  views  may  appear 
dogmatic,  it  must  be  remembered  that  we  are  unable, 
owing  to  limitation  of  space,  to  give  the  results  ob- 
tained by  different  observers,  but  must  content  our- 
selves with  an  expression  of  the  views  which  have 
obtained  more  or  less  general  assent. 

We  have  mentioned  in  previous  chapters  that  an 
intimate  relation  exists  between  many  of  the  sexual 
secretions  and  the  hormones  elaborated  by  some  of  the 
other  ductless  glands.  As  an  example,  the  adrenals 
have  an  intimate  relation  with  the  ovaries  and  testes, 

190 


THE  SEXUAL  OKGANS  191 

and  more  than  a  few  cases  are  recorded  which  bear 
this  out.*  Elliott  mentions  the  case  of  a  young 
woman,  perfectly  normal  sexually,  who  at  the  age 
of  twenty  lost  her  menses;  this  was  followed  by  the 
appearance  of  secondary  sexual  characteristics  of  the 
opposite  sex,  such  as  the  growth  of  a  beard  and  the 
development  of  a  masculine  type.  Four  years  later 
she  was  operated  upon  and  a  tumour  of  the  right 
adrenal  gland  removed.1 

Again,  a  case  described  by  Alberti  shows  a  similar 
relationship,  only  the  perversion  is  differently  con- 
nected. The  patient  was  a  young  girl  who  was  per- 
fectly normal  sexually,  but  who  gradually  reverted  to 
the  masculine  type.  There  was  a  loss  of  adipose  tissue, 
the  hair  increased,  more  especially  upon  the  body,  the 
breasts  became  soft,  and  the  voice  deepened.  A  few 
years  later  she  was  operated  upon  for  ovarian  tumour, 
and  eventually  died  of  peritonitis.  These  two  examples 
are  selected,  for  they  refer  to  relations  between  two 
different  systems,  and  show  that  an  intimate  relation- 
ship does  exist  between  the  sexual  glands  and  other 
of  the  internal  secretory  organs. 

Internal  Secretion  of  the  Testis. 

Eecent  experiments  have  shown  that  the  internal 
secretion  of  the  testis  has  a  vast  influence  in  animals 
belonging  to  the  species  which  has  a  periodical  rutting 
season,  for  changes  in  various  parts  of  the  body  as  well 

*  See  Chapter  I.,  p.  32. 


192   THE  ORGANS  OF  INTERNAL  SECRETION 

as  in  the  reproductive  organs  have  been  noticed  at 
such  times.  If  there  is  an  internal  secretion  provided 
by  the  testis  and  the  ovary,  where  is  this  formed  ?  It 
is  now  believed  that  the  "  interstitial  cells  of  Ley  dig  " 
in  the  testicle,  and  the  corresponding  cells  in  the 
ovarian  stroma,  are  the  sites  where  this  secretion  is 
manufactured. 

The  interstitial  cells  are  found  between  the  semin- 
iferous tubules,  and  vary  in  number.  They  are  of 
mesodermal  origin  and  appear  at  an  early  date  of 
embryonic  development,  before  the  seminal  cells  have 
assumed  their  cytological  character  (Biedl).  From 
the  study  of  the  development  of  sexual  characteristics 
in  cases  of  double  cryptorchidism,  from  the  effects  of 
ligature  of  the  vasa  deferentia,  and,  from  the  study  of 
tumours  developing  in  the  testis,  it  is  believed  that  the 
interstitial  gland,  or  organ  of  Leydig,  is  concerned  in 
the  production  of  the  internal  secretion  of  the  testis 
and  in  the  determination  of  the  male  sex  characteristics. 
"It  is  evident,  then,  that  the  presence  or  absence  of 
Sertoli's  cells  does  not  affect  the  secondary  sex  charac- 
ters, and  that  the  internal  secretory  function  is  the  sole 
property  of  the  interstitial  gland.  This  gland  not  only 
exercises  a  protective  influence,  but  it  determines  the 
appearance  of  the  somatic  male  characteristics."* 

The  changes  which  appear  at  puberty  owe  their 
origin  to  an  internal  secretion  which  "  sensitizes  "  the 
nervous  reflexes  concerned  with  the  performance  of 

*  Biedl,  "  The  Internal  Secretory  Organs,"  pp.  394,  395. 


THE  SEXUAL  ORGANS  193 

the  sexual  act.  That  the  various  nervous  reflexes  are 
developed  to  a  high  degree  of  sensitiveness  has  been 
shown  by  experiments  on  frogs  during  the  spawning 
season,  which  proved  conclusively  that  these  animals 
develope  additional  nervous  mechanisms  during  the 
period  of  sexual  activity. 

Again,  it  has  been  abundantly  established  that  a 
large  number  of  internal  secretions  are  concerned  in 
the  development  of  the  sexual  glands;  for  sexual  pre- 
cocity can  be  associated  with  tumours  of  the  adrenals 
and  with  disturbances  in  the  hormonic  balance;  while 
the  influences  upon  sexual  development  which  are 
exerted  by  the  hypophysis  have  already  been  dis- 
cussed in  a  previous  chapter.2*  It  would  seem,  how- 
ever, that  the  adrenal  gland  is  especially  concerned 
with  the  regulation  of  the  sexual  secretions,  for,  in 
some  post-mortem  examinations  of  cases  of  sexual 
precocity,  out  of  seventeen  such  cases,  and  four  surgical 
cases,  suprarenal  tumours  were  found  in  eleven,  nine 
being  girls  and  two  boys.3  There  are  many  more  such 
cases  which  have  been  published  which  certainly 
justify  us  in  assuming  that  the  relation  between  the 
genital  glands  and  the  chromaffin  system  is  a  close 
one,  and  morphologically  this  is  to  be  expected.4 

*  "  Souza  and  Castro  offer  an  excellent  study  of  the  diseases 
produced  by  endocrine  disfunctioning,  in  which  the  main  symp- 
toms are  atrophy  of  the  gonads  and  general  trophic  alterations. 
Their  observations  comprise  twenty  cases.  The  common  link 
of  them  is  atrophy  of  the  sexual  organs.  Three  of  the  cases 
had  tumours  of  the  pituitary  body  "  (Endocrinology,  p.  535). 

13 


194   THE  ORGANS  OF  INTERNAL  SECRETION 

The  Uterus  and  Mammary  Gland. 

Now  for  a  few  words  about  the  relation  between 
the  uterus  and  the  mammary  gland.  There  can  be 
little  doubt  that  the  development  of  this  latter  organ 
depends  upon  a  secretion  from  the  genital  apparatus. 
It  was  at  one  time  thought  that  the  connection  between 
the  uterus  and  the  breast  was  a  nervous  one;  but 
this  has  long  since  ceased  to  be  believed,  as  experi- 
ments have  shown  that  destruction  of  the  nervous 
connection  has  no  influence  in  inhibiting  the  flow  of 
milk  in  a  pregnant  animal.  The  connection  is  there- 
fore by  means  of  a  chemical  messenger;  and  it  is 
now  believed  that  this  messenger  emanates  from  the 
ovaries,  and  not  from  the  uterus,  as  was  formerly 
supposed.  Experiments  have  shown  that  the  mam- 
mary gland  does  not  develope  after  removal  of  the 
ovaries  in  young  animals,  but  that  transplantation  of 
ovarian  substance  produces  normal  development. 

Much  work  has  been  done  recently  upon  the  relation 
between  the  mammary  gland  and  the  pregnant  uterus. 
The  question  to  be  solved  is,  From  what  source  comes 
the  hormone  which  activates  lactation  ?  Is  it  from 
the  maternal  or  the  foetal  organs  ?  Does  it  come,  as 
maintained  by  Halban,  from  the  placenta,  or  does  the 
foetus  provide  it,  or  is  it  a  product  of  the  uterus  or 
ovary  ?  We  have  not  space  to  enter  into  the  details 
of  the  physiological  work  which  has  been  done  on  this 
subject;  we  must  therefore  content  ourselves  with  out- 
lining the  views  of  authorities. 


THE  SEXUAL  OEGANS  195 

Basch,  from  the  results  of  experiments  in  which  he 
injected  placental  extracts,  came  to  the  conclusion  that 
mammary  activity  during  pregnancy  depended  upon 
a  substance  found  in  the  placenta.  Starling  and  Lane- 
Claypon  experimented  with  injections  of  foetal  extract, 
extract  of  uterine  mucous  membrane,  and  ovarian 
extract.  They  produced  mammary  hyperplasia  by 
injecting  fcetal  extract,  but  the  other  extracts  were 
inert  in  this  respect.  This  has  been  confirmed  by 
experiments  carried  out  by  Foa,  and  also  by  Biedl  and 
Konigstein. 

Without  entering  into  any  further  details  of  these 
experiments,  we  may  quote  in  full  the  conclusion  at 
which  Biedl  arrives  on  this  subject,  for  it  gives  a  good 
hypothesis  upon  which  to  base  our  views.  "  The 
secretion  of  the  hyperplastic  mammae  is  not  difficult  of 
explanation.  .  .  .  The  growth  of  the  gland  is  the 
expression  of  an  assirnilatory  increase  of  material  with 
simultaneous  inhibition  of  disassimilatory  decomposi- 
tion. The  growing  gland  produces  no  secretion,  or 
very  little  (colostrum).  With  the  suppression  of  the 
assirnilatory  hormone  supplied  by  the  fcetus — that  is 
to  say,  at  birth  or  by  termination  of  the  pregnancy 
during  the  second  half — disassimilatory  decomposi- 
tion, as  expressed  by  the  secretion,  is  enabled  to 
proceed  unchecked."6 

We  need  not  spend  much  time  in  studying  the  effects 
of  castration  upon  development,  for  these  are  well 
known.  There  are,  however,  one  or  two  facts  which 
are  important. 


196   THE  ORGANS  OF  INTERNAL  SECRETION 

Effects  of  Castration. 

The  removal  of  the  ovaries  in  young  animals  pro- 
duces certain  features  of  arrested  development,  among 
these  being  a  rudimentary  condition  of  the  Fallopian 
tubes  and  uterus.  It  has  been  shown,  however,  that 
the  transplantation  of  ovarian  tissue  under  the  skin 
remedies  all  these  defects  and  the  animal  developes 
normally.  This  shows  definitely  that  the  controlling 
influence  is  chemical  (hormonic),  and  not  reflex.  Again, 
the  effects  of  castration  upon  young  male  animals,  and 
upon  youths,  as  is  practised  in  the  East,  shows  that 
there  is  a  definite  controlling  agent  in  the  secretion  of 
the  genital  glands  which,  directly  or  indirectly,  governs 
growth.  Thus,  changes  take  place  in  the  bones,  par- 
ticularly in  the  skull  and  the  pelvis,  which  produce  an 
increase  of  growth,  with  retarded  ossification  of  the 
epiphyses. 

Pregnancy  appears  to  be  accompanied  by  reduced 
ovarian  section,  and  it  has  been  noted  that  young 
females  grow  during  pregnancy,  which,  accompanied  as 
it  is  by  diminished  ovarian  secretion,  would  appear  to 
show  that  the  restraining  influence  of  this  secretion  is 
temporarily  removed.  Or,  to  put  it  in  another  way, 
the  sexual  glands  elaborate  a  hormone  which  is  con- 
cerned in  the  ossification  of  epiphyses;  if  this  be  with- 
drawn before  ossification  is  complete,  increased  skeletal 
growth  ensues. 

Again,  castration  affects  the  hormonic  balance,  as 
is  shown  in  the  changes  which  are  produced  in  the 


THE  SEXUAL  OEGANS  197 

thyroid,  thymus,  pituitary,  etc.,  by  removal  of  the 
testes:  and  Fichera  showed,  in  1906,  that  the  enlarge- 
ment of  the  pituitary  which  followed  castration  in 
animals  could  be  reduced  by  the  injection  of  extract 
of  the  testicle.  Again,  it  has  been  shown  that  the 
thyroid  under  such  conditions  is  atrophied,  the  thymus 
persistent,  and  the  hypophysis  enlarged.  Only  a  few 
experiments  have  been  performed  on  this  aspect  of  the 
relationship  of  the  genital  glands  with  other  of  the 
organs  of  internal  secretion ;  but  in  one  instance  of 
a  eunuch  dissected  by  Tandler  and  Gross  these 
changes  in  the  thyroid,  thymus,  and  pituitary,  were 
noted. 

Again,  the  general  metabolism  is  profoundly  affected 
by  changes  in  the  reproductive  organs ;  and  the  obesity, 
and  in  some  cases  mental  sluggishness  or  other  psychic 
changes  which  occur  in  senility,  are  too  well  known  to 
require  more  than  mention.  Lowy  and  Richter  in- 
vestigated the  metabolism  in  castrated  animals,  and 
showed  that  there  was  a  reduction  in  proportion  to 
body-weight,  as  well  as  a  reduction  in  the  total  meta- 
bolism of  the  body.* 

*  Some  experiments  recorded  by  Wheelon  and  Shipley  are 
instructive.  The  object  in  view  was  to  demonstrate  the 
relationship  between  the  sympathetic  nervous  system  and  the 
internal  secretion  of  the  testis.  These  experiments  showed 
that  about  six  weeks  after  castration,  pressure  responses  to 
nicotine  averaged  50  per  cent,  lower  than  before  removal  of  the 
testis.  From  two  to  three  weeks  after  a  testicular  transplant 
there  was  a  marked  rise  in  the  activity  of  the  vasomotor 
mechanism.  "  The  findings  point  to  the  conclusion  that  a 
direct   relationship    exists    between   the   sympathetic    nervous 


198   THE  OEGANS  OF  INTEKNAL  SECRETION 

The  relation  between  ovarian  secretion  and  osteo- 
malacia has  been  the  subject  of  much  speculation. 
Biedl  thinks  that,  while  it  cannot  be  maintained  that 
we  have  definite  proof  of  the  causative  role  played  by 
the  ovarian  secretion  in  the  production  of  this  disease 
the  probability  is  that  the  ovary,  rather  than  any  of 
the  other  endocrine  glands,  such  as  the  thyroid, 
thymus,  etc.,  is  the  main  gland  concerned  in  the  pro- 
duction of  the  disease;  although  there  may  be  several 
glands  concerned,  the  ovary  is  certainly  the  chief. 

The  pioneer  work  which  Brown- Sequard  undertook 
in  administering  to  himself  extracts  of  testicles,  and 
the  report  which  he  made  as  to  the  results,  may  be 
said  to  have  founded  the  theory  and  practice  of  organo- 
therapy, however  empirical  this  treatment  was  and, 
to  a  certain  extent,  still  is.  His  results  are  very  well 
known,  and  need  not  be  stated  here  at  any  length; 
suffice  it  to  say  that  he  found  his  strength  much  in- 
creased by  this  administration,  he  was  less  liable  to 
fatigue,  his  excretory  apparatus  was  improved,  and 
the  effects  were  in  general  satisfactory.  Testicular 
extract  is  said  to  contain  nucleoprotein  and  toxic 
bases,  and  it  has  been  stated  by  some  observers  that 
the  results  of  administering  such  an  extract  to  animals 
are  widespread  and  important;*  also  it  has  recently 

system  and  the  primary  reproductive  organs.  Castration 
results  in  a  depression  of  the  sympathetic  mechanism,  while  the 
re-establishment  of  the  lost  parts  partialty  reinstates  normal 
activity  "  (Author's  Abstract  in  Endocrinology,  pp.  482,  483). 

*  I  have  recently  received  some  reports  of  clinical  experience 
with  these  extracts,  which  emphasize  one  aspect  of  their  ad- 


THE  SEXUAL  OKGANS  199 

been  said  to  play  a  part  in  the  production  of  the 
genito-vesicular  reflex  (Serralach  and  Pares,  quoted 
by  Biedl).  On  the  other  hand,  it  has  been  stated  that 
ovarian  extract,  when  injected,  lowers  blood-pressure, 
causes  in  the  thyroid  gland  a  preliminary  reduction 
followed  by  an  enormous  increase  in  volume,  and 
reduces  the  volume  of  the  kidney. 


The  Internal  Secretions  o£  the  Sexual  Organs. 

As  we  have  already  said,  the  cells  of  Leydig  are 
supposed  to  be  the  seat  of  formation  of  the  internal 
secretion  of  the  testis;  and  an  interesting  fact  in  con- 
nection with  this  is  that  puberty  produces  an  enormous 
development  of  these  cells,  while  old  age  sees  a  marked 
degree  of  atrophy  of  the  same  cells.  It  is  stated  that, 
in  those  cases  where  cryptorchidism  in  man  is  asso- 
ciated with  the  development  of  secondary  feminine 
characteristics,  there  is  complete  sclerosis  of  the 
testicle,  and  that  the  cells  of  Leydig  are  reduced  to  a 
few  scanty  groups  (Biedl). 

The  influence  which  the  ovarian  internal  secretion 
exerts  may  be  studied  from  two  standpoints:  first,  its 
place  in  determining  the  sex  characteristics,  and 
second,  its  relation  to  other  bodily  hormones. 

It  has  usually  been  acknowledged  that  the  secretions 


ministration — namely,  that  they  are  liable  to  increase  the  blood- 
pressure.  If  this  experience  is  confirmed,  their  utilization 
should  be  accompanied  by  a  careful  scrutiny  of  the  vascular 
system. 


200   THE  OEGANS  OF  INTERNAL  SECRETION 

of  the  gonads  determine  the  sex  characteristics,  and 
that  the  menstrual  cycle  is  regulated  by  hormones 
which  are  secreted  by  the  ovaries.  In  animals  it  has 
been  shown  that  the  catamenia  occurs  when  the  ovaries 
are  transplanted  (Marshall  and  Jolly),  which  indicates 
that  this  function  is  not  regulated  by  nervous  controls. 
Again,  experiments  have  proved  that  oestrus  occurs  in 
animals  in  whom  the  spinal  cord  has  been  divided,  and 
a  case  is  on  record  in  which  a  woman  became  pregnant 
with  complete  transverse  lesion  of  the  spinal  cord. 

In  speaking  of  the  influence  of  the  ovary  on  the  sex 
characteristics,  Blair  Bell  says:  "  ...  It  is  commonly 
held  that  the  genital  organs,  and  more  particularly  the 
gonads,  contribute  the  primary  sex  characteristics,  and 
that  the  secondary  sex  characteristics  are  dependent 
on  internal  secretions  arising  from  the  gonads  in 
question — male  or  female  as  the  case  may  be.  .  .  . 
It  is  well  known  that  every  person  is  partly  masculine 
and  partly  feminine,  that  in  each  case  are  to  be  found, 
especially  in  connection  with  the  genital  ducts,  relics 
of  the  opposite  sex,  and  that  during  the  first  few  weeks 
of  foetal  life  it  is  not  possible  to  identify  the  trend  of 
sex  development.  .  .  .  About  the  end  of  the  fifth 
week  of  foetal  life  it  may  be  possible  to  decide  whether 
the  gonad  is  to  be  an  ovary  or  a  testis;  hitherto  it  has 
been  an  indifferent  organ,  so  much  so  that  the  cause 
of  development  in  the  Gartnerian  (primary  excretory) 
and  Miillerian  ducts,  especially  in  the  latter,  may  give 
the  first  indication  of  sex  determination.  ...  It 
appears   probable,   therefore,   that   normally  the  sex 


THE  SEXUAL  OKGANS  201 

development  of  the  ducts  is  not  primarily  dependent 
on  the  nature  of  the  gonad.  In  other  words,  the 
character  of  the  sex  pervades  all  the  tissues  of  the 
foetus,  including  the  sex  gland  itself."* 

The  relation  of  the  ovarian  secretion  to  other  internal 
secretions  is  intimately  mixed  up  with  the  influence 
of  the  gonads  in  general  upon  metabolism,  and  this  we 
have  already  discussed. f  It  is  not  too  much  to  say 
that  the  ovarian  secretion  is  of  vital  importance  to  the 
individual,  both  from  the  mental  and  physical  stand- 
point; and  in  this  relation  the  ovary  is  analogous  to 
the  testis.  We  have  already  seen  that  changes  are 
produced  in  such  distant  organs  as  the  thyroid,  thymus, 
and  pituitary,  by  removal  of  the  testes,  and  similar 
results  are  noted  after  removal  of  the  ovaries.  After  the 
normal  menopause,  which  is  usually  gradual,  changes 
similar  in  character  take  place,  and  Blair  Bell  is  of  the 
opinion  that  ;i  the  more  sudden  the  climacteric  the 
worse  the  effect. "J 

The  influence  of  the  ovarian  secretion  upon  the 
mammary  development  is  more  marked  before  puberty 
than  after,  castration  before  puberty  preventing 
glandular  development.  The  inter-relationship  of  the 
gonads  with  the  other  internal  secretions  forms  one  of 
the  most  interesting  albeit  intricate  problems  of  endo- 
crinology.    We  have  already  glanced  at  these  rela- 

*  "  An  Address  on  the  Nature  of  the  Ovarian  Function,"  by 
W.  Blair  Bell.     Lancet,  October  30,  1920,  pp.  879,  880. 
t  Chapter  I. ;  see  also  preceding  pages. 
X  Loc.  cit.,  p.  881. 


202   THE  OEGANS  OF  INTERNAL  SECRETION 

tionships,  but  perhaps  we  may  enlarge  somewhat  in 
this  chapter  upon  the  action  and  interaction  of  the 
gonads  and  the  other  hormones. 

Oophorectomy  produces  changes  in  almost  all  the 
ductless  glands.  In  animals,  before  puberty,  it  results 
in  mal- development  of  the  uterus,  and  disease  or 
removal  of  the  ovaries  is  usually  accompanied  by  loss 
of  the  feminine  characteristics,  and,  in  some  cases,  the 
development  of  male  features.  It  would  seem,  there- 
fore, that  there  are  potentially  male  characteristics 
which  remain  latent  so  long  as  the  ovarian  secretion 
is  active.  The  experiments  of  Marshall  and  Jolly 
throw  further  light  upon  the  importance  of  this  secre- 
tion to  the  normal  menstruation.  These  observers 
showed  that  if,  after  oophorectomy,  part  of  the 
ovarian  substance  is  transplanted,  the  tissues  may 
survive  and  atrophy  of  the  uterus  does  not  occur. 
Ova  may  be  formed  and  menstruation  continue.  The 
grafts  are  more  successful  if  the  tissue  comes  from  the 
animal  itself,  rather  than  from  another  animal. 

Steinach's  observations  on  rats  show  that  the 
ovarian  tissue  plays  an  important  part  in  the  formation 
of  the  femininity  of  the  body.  He  transplanted  ovarian 
tissue  into  young  castrated  male  rats,  producing  the 
"  characteristic  slight  bony  development,  the  growth 
of  the  finer  hair  of  the  female,  the  development  of 
mammae  and  nipples,  and  the  appearance  of  two 
peculiar  female  reflexes:  (1)  'The  tail  erect  reflex'; 
and  (2)  the  peculiar  kicking,  guarding  reflex  to  keep 
the  male  off  before  the  full  development  of   oestrus. 


THE  SEXUAL  ORGANS  203 

These  feminized  rats  were  followed  by  males  as  if  they 
were  female."* 

The  effects  of  removal  of  the  ovaries  upon  metab- 
olism in  general  are  widespread.  There  is  a  decrease 
in  the  respiratory  exchanges  of  14  to  20  per  cent.;f 
the  normal  is,  however,  restored  by  the  administration 
of  ovarian  extracts.  Adiposity  develops,  the  thyroid 
undergoes  change,  "  the  sympathetic  control,  too, 
always  somewhat  unstable  in  women,  becomes  more 
variable  owing  to  the  changes  that  take  place  in  the 
calcium  metabolism,  which  is  so  largely  concerned  in 
the  reproductive  processes.  "J 
"~"~The  thyroid  appears  to  assist  the  gonads,  for  thyroi- 
dectomy arrests  their  growth.  The  pituitary  has  a 
similar  relation,  for  its  destruction  produces  atrophy 
of  the  sex  glands;  inversely  castration,  it  should  be 
noted,  causes  pituitary  hypertrophy.  Reference  has 
already  been  made  to  the  close  relationship  existing 
between  the  adrenal  bodies  and  the  gonads,  and  we 
have  quoted  the  views  of  Sajous  on  the  part  played  by 
adrenal  tissue  in  regulating  the  sexual  functions. 
We  have  also  indicated  the  metabolic  disturbances 
which  follow  castration,  and  drawn  attention  to  the 
resemblance  between  these  and  the  general  features 
of  hypothyroidism  and  hypopituitarism.  The  relation 
between  the  thymus  and  the  ovary  is  less  clear  than 
that  existing  between  the  former  gland  and  the  testis — 
namely,  a  supplementary  action.    The  thymus  exercises 

*  Noel  Paton,  "  Regulators  of  Metabolism,"  p.  153. 
t  Ibid.,  p.  161.  %  Blair  Bell,  loc.  cit.;  p.  882. 


204  THE  OEGANS  OF  INTERNAL  SECRETION 

a  controlling  action  on  the  gonads,  but  it  co-operates 
with  the  latter  in  stimulating  growth  and  development. 

There  is  a  suggested  relationship  between  the  para- 
thyroids and  the  gonads,  as  the  symptoms  of  hypo- 
parathyroidism are  increased  by  pregnancy  (Paton). 

Without  going  farther  into  the  physiology  of  the 
gonads,  it  is  sufficient  to  say  that  there  can  be  very 
little  doubt  that  these  organs  play  a  vital  part  in  the 
production  of  secretions  which,  although  we  are  igno- 
rant of  their  full  importance,  are  necessary  for  the 
development  of  a  normal  individual :  not  only  in  so  far 
as  sexual  characteristics  are  concerned,  but  even  with 
regard  to  the  adequate  working  of  metabolism. 

The  secretions  of  the  prostate  are  likewise  not  fully 
understood,  certainly  so  far  as  its  internal  secretion  is 
concerned.  Its  external  secretion  exerts  an  influence 
upon  the  spermatozoa,  and  dilutes  the  testicular  fluid; 
but  little  is  known  of  the  properties  of  its  hormone, 
except  that  injections  of  prostatic  extract  made  from 
animals  are  extremely  toxic.  Therapeutically,  extracts 
of  prostate  gland  are  not  prescribed  much  in  this 
country,  although  they  are  supposed  to  be  beneficial 
in  post-operative  melancholic  conditions  following 
removal  of  this  gland. 

Therapeutics  of  the  Sexual  Glands. 

We  must  now  turn  our  attention  to  the  therapeutic 
possibilities  of  extracts  of  the  genital  glands,  and  we 
shall  endeavour  to  give  a  resume  of  the  possibilities  of 
such  therapy. 


THE  SEXUAL  OEGAXS  205 

A  very  wide  range  of  treatment  is  open  for  the  ad- 
ministration of  preparations  made  from  the  gonads, 
and  it  is  now  established  that,  in  conjunction  with 
other  organo-therapeutic  preparations,  should  these  be 
indicated,  a  great  deal  of  benefit  may  accrue  to  patients 
suffering  from  a  variety  of  diseases  which  it  would  be 
difficult  to  ameliorate  by  other  means. 

Let  us  commence  our  study  by  considering  the  help 
which  may  be  given  to  that  very  widely  encountered 
disease,  neurasthenia.  It  has  been  conclusively  proved 
that  the  exhibition  of  some  preparation  of  the  testes 
(such  as  Spermin)  has  the  power  of  raising  the  amount 
of  muscular  work  available,  of  increasing  the  strength 
of  the  individual,  and  of  banishing  ready  fatigue.  In 
other  words,  the  conclusions  arrived  at  by  Brown- 
Sequard  have  been  substantiated,  and  it  is  now  be- 
lieved that  the  administration  of  testicular  prepara- 
tions is  followed  by  improvement  in  these  cases.  Some 
manufacturers  combine  this  substance  with  other  se- 
cretions in  the  form  which  Leonard  ^Yilliams  aptly 
calls  a  "  mitrailleuse." 

Unfortunately,  there  appears  to  exist  some  degree 
of  opposition  to  this  remedy,  and  in  consequence  it 
has  never  been  widely  used.  There  is,  however,  a  good 
deal  to  be  said  for  its  powers,  and  Harrower  sum- 
marizes its  utility  in  the  following  words: 

*'  A  course  of  treatment  with  testicular  extract  fre- 
quently accomplishes  such  a  number  of  changes  of 
such  remote  organs,  and  influences  such  widely  dis- 
connected ones,  that  to  report  actual  results    might 


206   THE  OEGANS  OF  INTERNAL  SECRETION 

even  be  sufficient  to  discount  the  position  of  this 
method.  The  extent  of  these  results  is  undoubtedly 
due  to  the  stimulating  action  of  the  testicular  hormone 
upon  the  endocrinous  system  as  a  whole,  and  as  a 
means  of  revitalizing  an  individual  with  deficient 
oxidation,  poor  nutrition,  nervous  inactivity,  and 
general  weakness,  the  system  is  of  undoubted  value. 
There  are  few  single  remedies  which  can  compare  with 
active  and  properly  prepared  testicular  extracts."6 

The  therapeutic  possibilities  of  the  ovaries  are 
numerous.  Thus,  it  is  well  known  that  an  intimate 
relation  exists  between  the  pituitary  gland  and  the 
ovaries,  and  consequently,  in  undertaking  the  treat- 
ment of  disorders  of  the  pituitary,  this  fact  should 
be  remembered.  The  administration  of  ovarian  ex- 
tract is  worthy  of  trial  in  such  cases,  more  specially 
where  the  symptoms  point  to  excessive  bony  growth 
(it  has  already  been  said  that  the  ovary  is  presumed  to 
exert  an  influence  on  the  ossification  of  the  epiphyses). 
In  this  connection  Blair  Bell,  speaking  of  imperfect 
development,  says: 

"  Nearly  all  the  patients  are  adipose,  whether  the 
deficiency  arise  in  the  thyroid,  pituitary,  or  ovaries. 
If  there  be  pituitary  insufficiency,  the  skin  will  be 
found  to  be  soft  and  smooth;  if  there  be  thyroid  in- 
sufficiency, it  is  harsh  and  rough.  With  pituitary 
insufficiency  the  blood-pressure  tends  to  be  below 
110  mm.  Hg;  but  with  thyroid  insufficiency  it  is 
usually  normal  (125  mm.  Hg),  or  slightly  above 
normal."7 

Further,  if  it  be  true  that  both  thyroid  and  pituitary 


THE  SEXUAL  OEGANS  207 

insufficiency  induce  ovarian  insufficiency,  then  we  can, 
as  Blair  Bell  points  out,  treat  the  ovarian  deficiency 
by  means  of  either  thyroid  or  pituitary  extract.  This 
simplifies  treatment  in  so  far  as  this  class  of  disorder 
is  concerned;  but,  nevertheless,  for  other  instances  of 
ovarian  deficiency,  such  as  are  exemplified  in  derange- 
ments of  the  catamenia,  ovarian  extract  will  be  found 
to  be  very  useful.  Blair  Bell  also  drew  attention  to 
the  influence  of  the  ovaries  upon  calcium  metabolism, 
and  showed  that  the  calcium  in  the  urine  was  dimin- 
ished after  oophorectomy  by  one-half;8  winch  again 
bears  out  what  we  know  with  reference  to  the  bene- 
ficial effects  which  sometimes  follow  in  cases  of  osteo- 
malacia when  double  oophorectomy  is  performed. 

Ovarian  extract  has  been  utilized  in  the  treatment 
of  such  disorders  as  chronic  rheumatism,  gout,  and 
fibrositis.  Psoriasis,  often  associated  with  such  diseases 
as  these,  has  been  treated  with  this  extract,  and  some 
authorities  have  claimed  good  results.  Some  degree 
of  correlation  has  been  noted  between  the  appearance 
of  psoriasis  and  the  alteration  in  the  regularity  of 
the  menstrual  flow. 

Harrower  says  that  better  results  are  obtained  by 
the  exhibition  of  extracts  of  the  corpus  luteum  than 
are  recorded  by  the  ingestion  of  extracts  of  the  whole 
gland;  and  other  observers  are  of  the  opinion  that  the 
superiority  of  this  extract  over  the  total  extract  of  the 
gland  is  incontrovertible.  Extract  of  corpus  luteum 
will  be  found  useful  in  neurasthenia  in  women,  in 
difficulties  arising  at  the  menopause,  after  removal  of 
the  ovaries  for  cystic  or  other  disease,  and  in  con- 


208   THE  ORGANS  OF  INTERNAL  SECRETION 

junction  with  tigroid  or  pituitary  for  incomplete 
development,  etc. 

Several  writers,  notably  Leduc  and  Blair  Bell,  lay 
great  stress  upon  the  calcium  metabolism  of  the  body, 
and  its  relation  to  disorders  of  the  nervous  system 
(neurasthenia,  hystero-epilepsy).  Thus,  we  know  that 
there  is  a  storage  of  calcium  salts  in  hypothyroidism, 
and  an  increase  in  the  calcium  metabolism  in  Graves' 
disease;  also  that  at  times  like  the  menopause  a  dis- 
turbance of  more  than  one  gland  may  take  place.  The 
signs  in  any  individual  case  may  point  to  which  of  the 
endocrinous  glands  is  chiefly  at  fault;  but  the  best 
results  are  probably  obtained,  as  Blair  Bell  points  out, 
by  the  administration  of  ovarian  extracts,  in  company 
with  whichever  of  the  other  glands  appears  to  be  at 
fault.  Again,  this  writer  suggests  that  the  mental 
depression  from  which  some  women  suffer  at  the  cli- 
macteric can  be  much  relieved  by  the  administration 
of  thyroid  extract.  This  in  itself  would  point  to  the 
thyroid  as  being  one  of  the  glands  deficient  in  secretion 
at  the  menopause. 

One  more  fact  in  connection  with  the  ovaries,  and 
we  can  pass  on  to  the  consideration  of  other  secretions. 
It  is  assumed  that  menorrhagia  may  be  due  to  exces- 
sive action  of  the  ovaries — i.e.,  hyper-oophorism,  with 
which  may  be  associated  hyperthyroidism.  If  this 
may  be  presumed  to  be  so  in  any  given  case,  it  is 
obviously  wrong  treatment,  and  may  even  do  harm, 
to  administer  ovarian  extracts;  for  the  same  reason 
extract  of  thyroid  gland  must  be  avoided.  On  the 
other  hand,  where  amenorrhcea  is  present,  especially 


THE  SEXUAL  OEGANS  209 

where  the  appearance  of  the  menses  at  puberty  is 
delayed,  we  may  with  advantage  prescribe  thyroid 
extract  with  or  without  ovarian  extract,  remembering 
the  stimulating  effect  which  this  extract  exerts  upon 
this  function.  Therefore,  where  obesity  is  associated 
with  amenorrhcea  the  possibility  of  hypo-oophorism 
should  be  borne  in  mind. 

We  must  refer  in  passing  to  the  mammary  gland, 
and  state  briefly  the  modern  conception  as  to  its  utility 
as  a  therapeutic  agent.  We  have  already  pointed  out 
that  Starling  and  Lane-Claypon  experimented  with 
foetal  extracts,  and  came  to  the  conclusion  that  such 
extracts  were  capable  of  producing  hyperplasia  of  the 
mammae.  Therefore  it  would  seem  from  this  that  the 
foetus  is  the  seat  of  formation  of  a  hormone  which 
stimulates  the  secretion  of  the  breasts.  That  there  is 
a  close  relation  between  the  uterus  and  the  mammary 
gland  has  been  known  for  a  long  time;  what  that 
relation  is  we  are  better  able  to  say  now  than  formerly. 
The  obvious  connection  between  the  functioning  of 
the  breast  and  the  uterus  is  exemplified  by  such 
occurrences  as  the  enlargement  of  the  mammae  at 
puberty  and  pregnancy,  the  intimacy  of  its  nerve 
connections,  and  the  pain  in  the  breasts  during  men- 
struation. The  following  facts  also  bear  upon  this 
study:  the  placental  hormone,  to  which  we  have 
already  referred,  when  injected  into  another  animal, 
produces  a  flow  of  milk;  and  this  will  likewise  take 
place  in  transplanted  portions  of  the  gland. 

The  relation  of  the  ovary  to  the  mammary  gland 

14 


210  THE  OKGANS  OF  INTERNAL  SECRETION 

has  something  in  its  bearing  of  an  antagonistic  nature. 
Thus,  although  complete  ovariotomy  may  result  in 
disappearance  of  the  breasts,  which  latter  glands  will 
reappear  upon  grafting  ovarian  tissue,  some  observers 
believe  that  ovarian  secretion  is  antagonistic  to  mam- 
mary. In  this  connection  it  is  interesting  to  note  that 
some  investigators  have  found  that  the  rupture  of  the 
ripe  follicle  of  the  ovary  results  in  the  growth  of  the 
mammary  glands. 

From  the  therapeutic  standpoint,  moreover,  the 
balance  of  evidence  is  in  favour  of  administering 
mammary  extract  to  promote  lactation.  It  is  also 
stated  to  be  useful  in  combating  dysmenorrhcea  and 
menorrhagia;  it  is  not  improbable  that  it  is  able  to 
render  aid  to  the  uterine  functions,  either  on  account 
of  its  supposed  correlation  with  the  thyroid  gland,  or 
on  account  of  the  known  sympathy  which  exists 
between  the  mammae  and  the  uterus. 

We  have  now  outlined  the  facts  with  reference  to 
the  reproductive  glands  and  their  internal  secretions, 
and  we  have  indicated  the  lines  along  which  treatment 
of  these  disorders  may  be  conducted. 

References. 

1  Elliott,  Practitioner,  vol.  xciv.,  No.  1,  p.  132. 

2  Chapter  L,  pp.  31,32. 

3  Biedl,  The  Internal  Secretory  Organs,  p.  371. 

4  Chapter  I.,  p.  32. 

5  Biedl,  loc.  tit.,  p.  376. 

6  Harrower,  Practical  Hormone-Therapj7,  p.  341. 

7  Blair  Bell,  Practitioner,  vol.  xciv.,  No.  2,  p.  270. 

8  Blair  Bell,  The  Genital  Functions  of  the  Ductless  Glands 
in  the  Female,  Lancet,  1913,  i.  809. 


CHAPTEE  X 
THE  INTERNAL  SECRETIONS  OF  DIGESTION 

No  book  dealing  with  the  ductless  glands  and  their 
internal  secretions  would  be  complete  without  due 
reference  to  the  part  played  by  chemical  messengers 
in  the  processes  of  digestion.  For  while  our  knowledge 
in  this  field  is  very  incomplete,  we  know  now  that 
many  of  the  factors  which  contribute  to  normal 
digestion  are  chemical,  and  not,  as  was  thought, 
nervous  in  origin.  It  was  previously  assumed  that 
the  functions  of  digestion  were  regulated  by  either 
the  sympathetic  or  central  nervous  system,  and  the 
influence  of  hormones  was  unrecognized.  But  recent 
work  on  digestion  has  shown  that  even  in  this  field 
the  work  performed  by  autacoids  is  by  no  means 
unimportant. 

For  this  reason,  therefore,  we  propose  to  discuss 
briefly  the  internal  secretions  concerned  in  digestion, 
and  to  outline  the  main  features  of  their  work.  We 
shall  also,  wherever  possible,  draw  attention  to  any 
relationships  which  may  be  presumed  to  exist  between 
the  organs  of  digestion  and  other  glandular  structures 
of  the  body. 

The  salivary  glands  have  been  supposed  to  secrete 

211 


212   THE  ORGANS  OF  INTERNAL  SECRETION 

a  hormone  which  plays  a  part  in  digestion,  either  by 
stimulating  the  later  stages  of  digestion  or  by  carrying 
on  salivary  digestion  in  the  stomach.  There  is  now 
no  doubt  that  this  stage  of  digestion  continues  in  the 
stomach,  certainly  in  that  part  of  the  bolus  which 
remains  alkaline — that  is  to  say,  until  it  is  soaked 
through  with  the  gastric  juices;  and  therefore  the 
main  work  performed  by  the  ferment  may  be  said  to 
be  carried  on  in  the  stomach. 

Again,  certain  authorities  lay  stress  upon  the  parotid 
juice,  and  the  possibility  that  it  may  be  influenced 
by  chemical  messengers;  while  some  clinicians  have 
worked  with  preparations  of  the  salivary  glands, 
and  have  reported  that  they  have  influenced  some  of 
the  abnormal  conditions  arising  in  other  and  remote 
organs.  Thus,  they  have  been  used  for  ovarian 
disorders  (the  close  connection  existing  between  the 
parotid  gland  and  the  gonads  is  shown  by  the  meta- 
static inflammations  arising  in  the  course  of  parotitis 
in  the  testicles  and  ovaries),  and  have  been  said  to  do 
good.  Apart  from  this,  which  we  have  mentioned  in 
passing,  there  is  no  evidence,  not  even  presumptive, 
that  the  salivary  glands  are  useful  from  the  thera- 
peutic standpoint. 

The  Gastric  and  Intestinal  Secretions. 

When  we  turn  to  the  question  of  gastric  and  duo- 
denal digestion,  we  find  that  we  are  at  once  in  quite 
a   different   position.     At   the   risk  of   wearying  our 


INTERNAL  SECRETIONS  OF  DIGESTION    213 

readers,  we  will  briefly  recapitulate  the  work  which 
led  to  the  important  discovery  that  pancreatic  diges- 
tion is  dependent  upon  chemical  stimulation. 

Following  upon  the  researches  of  certain  observers, 
it  was  discovered  that  the  introduction  of  dilute  hydro- 
chloric acid  into  the  alimentary  canal  was  followed 
by  a  marked  increase  in  pancreatic  secretion;  that  this 
was  due  to  the  acid  coming  into  contact  with  the  walls 
of  the  duodenum;  and  that  this  produced  a  hormone 
which  possessed  the  property  of  stimulating  pancreatic 
secretion.  It  was  the  discovery  of  this  last  factor, 
a  discovery  made  by  Bayliss  and  Starling  in  1902, 
which  may  be  said  to  have  laid  the  foundation  of  our 
present  knowledge  of  the  importance  of  the  chemical 
messenger  in  keeping  that  balance  in  organic  meta- 
bolism which  alone  can  produce  perfect  health. 

This  substance  has  been  named  "  secretin"  and  is 
released  from  its  precursor  prosecretin  by  the  entrance 
into  the  alkaline  duodenum  of  the  acid  chyme.  This 
substance,  which  has  been  called  the  principal  ali- 
mentary hormone,  is  present  in  all  animals,  and  is  not 
only  a  human  property;  in  fact,  it  has  been  stated 
that  the  human  intestine  is  relatively  and  actually 
lower  in  its  secretin- content  than  is  that  of  the  sheep.1 
An  analogous  secretion  is  furnished  by  the  pyloric 
walls,  and  has  been  called  gastric  secretin  or  gastrin ; 
and  it  acts  upon  the  oxyntic  and  peptic  glands  of  the 
stomach.  Edkins  was  the  first  to  demonstrate  the 
presence  of  this  substance  in  the  stomach,  and  to  show- 
that  its  object  is  to  stimulate  into  activity  the  secreting 


214   THE  OKGANS  OF  INTERNAL  SECRETION 

cells  of  the  stomach.  This  hormone  has  a  precursor, 
known  as  pro-gastrin,  from  which  the  hormone  is 
formed,  either  by  the  products  of  digestion  or  by 
other  stimulus. 

In  this  way,  then,  do  we  find  that  a  chemical 
messenger  exists  to  activate  from  latent  chemicals 
an  active  substance;  and  that  in  both  cases — the 
gastric  and  the  duodenal — the  key  which  unlocks 
this  chemical  is  a  normal  and  usual  concomitant  of 
digestion.  In  the  case  of  the  duodenal  "  secretin," 
the  acid  unlocks  the  secretion  either  by  neutralizing 
a  substance  which  inhibits  the  flow  of  secretin,  or 
else  by  directly  producing  the  substance  "  secretin  " 
from  its  precursor  "  pro-secretin."  Whichever  is  the 
case  is  not  a  matter  which  need  detain  us  here,  and 
we  will  pass  on  to  discuss  other  properties  of  this 
important  hormone. 

It  appears  that  secretin  acts  not  only  on  the  upper 
intestinal  tract  in  producing  pancreatic  secretion,  but 
also  on  the  lower  intestinal  walls — i.e.,  the  ileum — 
and  assists  in  the  production  of  succus  entericus. 
It  likewise  stimulates  bile  production,  and  it  is  said 
that  the  typical  stools  of  jaundice  have  been  rendered 
normal  in  colour  by  a  few  doses  of  secretin.  In  this 
way,  therefore,  this  substance  may  be  regarded  as 
an  excitant  of  the  motor  functions  of  the  bowel;  for 
it  has  a  laxative  power  partly  dependent  upon  its 
action  upon  the  intestinal  juices  and  partly  owing 
to  its  action  in  increasing  the  normal  laxative,  the 
bile.     But   it   is    necessary   that    a    certain   element 


INTEKNAL  SECEETIONS  OF  DIGESTION    215 

should  be  present  in  the  blood,  for  Hustin  has  shown 
that  secretin  alone  is  incapable  of  stimulating  the 
pancreatic  juice  in  the  absence  of  blood.  '  The 
pro-secretin  of  the  duodenal  wall  is  first  changed  into 
secretin  by  contact  with  hydrochloric  acid;  it  is  then 
carried  in  the  blood-stream  to  the  pancreas,  where,  as 
a  result  of  chemical  change,  its  characteristic  features 
are  lost,  secretin  combining  with  amylopsinogen  and 
steapsinogen,  to  form  the  ferments  amylopsin  and 
steapsin,  and  with  the  precursor  protrypsinogen,  to 
form  trypsinogen.  This  last  becomes  the  ferment 
trypsin  only  after  it  has  come  into  contact  with  the 
entero-kinaise  in  the  intestinal  canal."*2 

It  will  be  seen  from  what  we  have  already  said 
that  the  acid  content  of  the  stomach  is  of  great  impor- 
tance in  the  production  of  the  secretion  of  the  pancreas, 
and  to  a  lesser  degree  of  the  other  intestinal  and  hepatic 
secretions.  It  will  also  be  seen  that  it  is  not  unlikely 
that  much  of  the  good  which  has  long  been  recognized 
to  accrue  from  the  prescription  of  acid  mixtures  in 
dyspeptic  and  constipated  subjects  may  in  reality,  as 
pointed  out  by  Harrower,  be  due  to  the  release  by 
such  acids  of  the  internal  secretions  of  the  bowel  and 
stomach.  The  hydrochloric  acid  of  the  gastric  mucosa 
has  several  important  functions  to  perform,  among 
these  being  its  work  as  an  antiseptic,  its  work  in 
opening  the  pyloric  sphincter,  its  power  to  activate 
pepsin,  and  lastly  its  action  as  a  stimulant  to   the 

*  Although  this  is  believed  to  be  the  sequence  of  events, 
there  is  still  some  divergence  of  opinion  on  the  subject. 


216  THE  ORGANS  OF  INTERNAL  SECRETION 

pancreatic  secretion.  In  its  absence  pancreatic  diges- 
tion cannot  be  carried  on,  for  secretin  cannot  be  formed 
from  pro-secretin. 

Although  the  facts  which  we  have  related  with  regard 
to  secretin  are  well  known  and  generally  admitted  as 
proven,  little  is  known  as  to  the  actual  constitution 
of  this  substance.  It  is  not  a  ferment,  but  exactly 
what  it  is  we  do  not  know.  It  is,  like  the  other  hor- 
mones, a  substance  of  low  molecular  weight,  and,  as 
we  have  already  seen,  it  stimulates  the  formation  of 
all  the  ferments  of  the  pancreas.  Its  work  in  the 
complex  scheme  of  digestion  is  balanced  to  a  nicety. 
Thus,  it  is  not  secreted  until  there  is  work  for  it  to 
do — in  other  words,  until  the  food  has  entered  the 
duodenum  in  its  acid  state;  thus,  there  is  no  chance 
that  it  will  irritate  the  walls  of  the  intestine  by  pro- 
ducing pancreatic  ferment-action  in  the  absence  of 
food.  Even  so,  trypsin  is  not  formed  until  it  meets 
entero-kinaise,  which  again  is  not  formed  until  food 
is  present. 

There  is  no  positive  evidence  that  secretin  stimulates 
the  internal  as  well  as  the  external  secretion  of  the 
pancreas,  for  it  has  yet  to  be  proved  that  there  is  an 
absence  or  diminution  of  secretin  in  diabetes.  In  fact, 
it  has  been  shown  in  one  case  of  diabetic  coma  that 
there  was  abundant  pro-secretin  in  the  body.3 

Turning  now  to  another  intestinal  secretion,  the 
succus  entericus,  there  is  still  some  question  as  to  its 
formation.  Pawlow  thinks  that  its  formation  depends 
upon  two  factors,  the  distension  of  the  bowel  and  the 


INTEENAL  SBOEETIONS  OF  DIGESTION    217 

presence  of  pancreatic  juice.  Succus  entericus  con- 
tains several  ferments :  entero-kinaise,  which  acts  upon 
the  trypsinogen  of  the  pancreatic  juice ;  erepsin,  which 
completes  the  digestion  of  proteids ;  and  several  sugar- 
splitting  ferments.  There  is  a  good  deal  of  dissension 
as  to  the  exact  nature  of  its  formation,  some  observers 
believing  that  it  acts  as  its  own  hormone,  others  that 
it  is  stimulated  by  the  pancreatic  juice,  while  others 
believe  that  additional  factors  other  than  those  men- 
tioned are  required  to  bring  about  the  secretion  of 
this  juice.  As  regards  the  proteolytic  action  of  the 
intestinal  juices,  these  latter  require  the  presence  of 
pancreatic  juice  to  exert  this  action. 

Turning  now  to  other  secretions  of  the  alimentary 
canal,  we  must  refer  in  passing  to  the  supposed  secre- 
tion of  the  appendix,  also  to  that  which  it  has  been 
suggested  emanates  from  the  lymphoid  tissue  of  the 
intestine,  such  as  Peyer's  patches.  Some  observers 
believe  that  the  appendix  secretes  a  hormone  which 
stimulates  peristalsis,  and  in  support  of  this  they 
quote  the  constipation  which  in  some  cases  follows 
the  removal  of  the  appendix  as  proof  that  a  normal 
intestinal  excitant  has  been  removed  or  inhibited. 
There  is  no  definite  proof  of  this,  although  the  future 
may  show  that  in  ruthless  appendicectomies  we  are 
removing  a  necessary  stimulant,  in  spite  of  the  fact 
that  so  many  regard  this  organ  as  a  useless  relic. 


218   THE  ORGANS  OF  INTERNAL  SECRETION 


The  Liver. 

The  liver,  whose  chief  function  is  the  production  of 
bile,  nevertheless  performs  many  other  and  important 
functions  which  contribute  to  the  normal  working  of 
the  body.  For  many  years  observers  have  been  struck 
by  the  enormous  size  of  this  gland,  which,  they  argued, 
could  hardly  be  justified  by  its  bile-producing  proper- 
ties alone.  This  was  before  its  storage  and  filtering 
functions  were  realized;  and,  even  after  the  facts 
collected  by  the  experiments  in  which  Eck's  fistula 
was  utilized,  much  remained  to  be  explained  as  to 
the  role  which  the  liver  played  in  bodily  metabolism. 
We  have  now  reached  the  stage  where  we  have  to 
consider  whether  the  liver  possesses  an  internal  secre- 
tion, and  whether  extracts  of  this  organ  can  be  utilized 
therapeutically. 

Let  us  first  summarize  the  functions  of  the  liver, 
and  with  the  facts  thus  gleaned  at  our  disposal  we 
shall  be  better  able  to  form  an  opinion  as  to  the 
secretions  produced  by  this  organ.  The  hepatic  cells 
are  responsible  for  the  production  of  the  bile,  with  the 
bile-salts,  pigments,  and  ferments;  they  are  also  con- 
cerned in  the  regulation  of  the  sugar  content  of  the 
blood,  and  in  the  regulation  of  nitrogenous  meta- 
bolism; they  are  concerned,  however,  in  regulating 
the  power  of  coagulation  of  the  blood,  and  they 
appear  to  have  a  definite  role  in  the  destruction  of 
toxins,  and  in  the  prevention  of  such  material  from 


INTERNAL  SECRETIONS  OF  DIGESTION   219 

reaching  the  cells  of  the  body.  In  this  latter  relation 
they  act  as  niters  between  the  gastro-intestinal  tract 
and  the  general  blood-stream. 

We  see,  therefore,  that  modern  physiology  teaches 
us  that  the  liver  has  other  functions  to  explain  its 
vast  size  beyond  the  mere  production  of  bile.  What 
evidence,  then,  have  we  that  it  possesses  an  internal 
secretion  ?  It  would  seem  that  the  secreting  powers 
of  the  liver  are  analogous  to  those  of  the  pancreas, 
inasmuch  as  they  depend  upon  stimulation  by  chemical 
means  for  the  adequate  working  of  their  secretions. 
This  has  been  shown  by  experiments  which  have 
proved  that  all  the  nerves  to  the  liver  can  be  cut 
without  interfering  with  the  biliary  secretions,  and 
that  excitation  of  the  cut  nerves  does  not  influence 
the  secretions  either  by  accelerating  or  retarding  such 
secretions.  We  saw  when  discussing  the  pancreatic 
secretion  that  it  was  stimulated  by  the  production 
of  secretin  from  pro -secretin  in  the  presence  of  the 
acid  chyme — i.e.,  that  it  was  dependent  upon  a  humoral 
messenger — and  in  like  manner  may  we  assume  that 
the  secretion  of  the  liver  is  affected.  Indeed,  we  know 
that  the  production  of  bile  is  increased  by  secretin, 
and  that  other  of  the  digestive  juices  are  stimulated 
by  this  same  hormone.  If  this  secretion  of  the  liver 
is  stimulated  by  a  hormone,  it  is  more  than  probable 
that  others  emanating  from  the  same  gland  are  also 
so  activated. 


220  THE  ORGANS  OF  INTEBNAL  SECRETION 

Therapeutics  of  the  Digestive  Secretions. 

The  extreme  value  of  cod-liver  oil  has  been  known 
for  many  years,  but  only  recently  has  it  been  recog- 
nized that  it  must  owe  its  power  to  something  more 
than  its  fat- content.  In  fact,  recent  work  has  shown 
that  some  of  its  value  can  be  removed  by  processes 
of  refining.  Leonard  Williams,  speaking  of  the 
properties  of  cod-liver  oil,  lays  stress  upon  this  aspect 
of  its  value,  and  says:  "...  it  is  very  probable  that 
this  biliary  secretion  of  the  cod,  when  introduced  into 
the  human  economy,  acts  as  a  stimulant  to  one  of 
the  normal  internal  secretory  glands,  and  that  the 
secretion  of  the  one  so  stimulated  is  inimical  to  the 
development  of  the  tubercle  bacillus.  .  .  ."4  This 
shows  us  another  reason  for  its  great  value  in  tubercu- 
losis, and  explains  its  power  of  building  up  the  body, 
while  preventing  toxins  from  reaching  remote  organs. 

Other  observers  have  experimented  with  cod-liver 
oil,  and  have  sought  to  show  that  it  is  not  the  animal 
fat  which  it  contains,  so  much  as  other  less  recognizable 
constituents,  to  which  it  owes  its  value.  The  internal 
secretory  theory  of  the  liver  extracts  certainly  opens 
the  way  to  many  new  applications  of  hormone-therapy 
and  also  explains  many  hitherto  unexplained  facts 
about  the  value  of  such  substances  as  cod-liver  oil. 

Here  we  must  leave  this  subject  and  pass  on  to  a 
brief  study  of  the  value  of  extracts  of  liver.  For  some 
years  such  extracts  have  been  used  on  the  Continent, 
and  many  observers  speak  highly  of  their  beneficial 


INTEENAL  SECEETIONS  OF  DIGESTION    221 

influence  in  countless  morbid  conditions.  Thus, 
Gilbert  and  Carnot,  of  Paris,  have  studied  this  subject 
intimately,  and  have  arrived  at  certain  conclusions 
about  this  organ  and  its  secretions.  Others,  following 
on  these  lines,  have  arrived  at  similar  conclusions, 
and  we  will  here  refer  briefly  to  one  of  the  theories 
about  the  liver  which  has  been  recently  expressed. 
Some  of  the  workers  in  this  subject  believe  that  the 
liver  possesses  an  internal  secretion  which  filters  the 
blood  coming  from  the  digestive  tract,  and  neutral- 
izes, or  renders  harmless,  toxins  emanating  therefrom. 
This  is  supposed  to  be  due  to  some  chemical  present 
in  the  liver  cells  itself,  and  not  only  in  the  blood- 
stream. In  this  way  the  liver  may  be  regarded  as  a 
vast  filter  standing  between  the  chemical  exchanges 
occurring  in  the  gastro-intestinal  tract — which  may 
possibly  be  harmful  if  admitted  into  the  systemic 
circulation  without  due  filtering — and  the  body.  It 
is  only  to  be  expected  that  the  organ  which  has  such 
important  work  to  perform  should  be  large,  and  these 
and  other  recent  views  (even  if  not  at  present  estab- 
lished beyond  criticism)  nevertheless  help  to  explain 
the  work  which  this  gland  is  called  upon  to  perform. 

Before  discussing  the  value  of  liver  extracts,  let  us 
consider  for  a  moment  the  therapeutic  properties  of 
secretin.  It  will  at  once  be  obvious  that,  provided 
this  chemical  can  be  prescribed  for  oral  administra- 
tion, and  that  wThen  taken  in  this  way  it  still  exerts 
its  characteristic  influence,  we  have  to  hand  a  remedy 
of  the  very  greatest  possibilities. 


222   THE  ORGANS  OF  INTERNAL  SECRETION 

Now,  it  appears  that  secretin-containing  prepara- 
tions can  be  so  prescribed,  and  that  they  are  active 
when  taken  by  the  mouth.  As  we  have  already  seen, 
secretin  requires  an  acid  medium  for  its  production 
and  that  in  the  absence  of  an  adequate  degree  of 
gastric  acidity  the  normal  secretion  of  this  substance 
cannot  take  place.  It  would  seem,  therefore,  that  in 
cases  where  hypochlorhydria  is  suspected,  especially 
where  secondary  digestive  disturbances  are  present, 
the  administration  of  an  acid  mixture  with  meals 
might  be  sufficient  to  insure  the  production  of  an 
adequate  amount  of  secretin. 

This  is  one  aspect  of  the  subject,  and,  there  can  be 
little  doubt,  an  important  one;  for  the  benefit  which 
so  often  accrues  from  an  acid  mixture  taken  about 
meal-times  is  frequently  out  of  all  proportion  to  what 
might  be  expected,  if  we  only  regard  it  as  an  adjuvant 
to  gastric  acidity. 

Another  question  which  arises  is,  Can  we  give 
secretin  by  the  mouth  ?  Undoubtedly  the  prepara- 
tions which  are  on  the  market  achieve  excellent 
results  in  many  cases,  and  the  dry  secretin-containing 
tablets  and  powders  appear  to  exert  a  beneficial 
action  in  a  wide  variety  of  cases,  which  range  from 
intestinal  meteorism  to  glycosuria.  But  the  dose  of 
the  substances  requires  regulating,  as  many  observers 
emphasize  the  fact  that  small  doses  often  succeed 
where  large  doses  fail. 

Secretogen,  which  the  makers  describe  as  "  the 
master-key  which  unlocks  the  alimentary  glands,"  is 


INTERNAL  SECRETIONS  OF  DIGESTION    223 

such  a  preparation,  and  many  excellent  results  have 
been  reported  after  its  use.  Again,  secretin  is  some- 
times combined  with  extracts  of  other  alimentary 
glands,  such  as  the  liver,  pancreas,  spleen,  etc. 

It  seems  to  the  present  writer  that  these  prepara- 
tions find  a  particular  field  of  usefulness  in  those  cases 
where  intestinal  symptoms  are  combined  with  signs 
indicative  of  pancreatic  or  hepatic  insufficiency. 
Thus,  intestinal  stasis  in  combination  with  glycosuria 
would  be  a  condition  where  a  secretin- containing 
preparation  might  improve  the  symptoms  in  a  quite 
remarkable  manner,  for  it  might  in  very  truth  "  un- 
lock "  the  duodenal  hormone  (or  replace  it  so  far  as 
its  pancreatic  stimulus  is  concerned),  and  thus  start 
the  alimentary  secretions,  stimulating  in  its  turn  the 
bile,  succus  entericus,  etc.,  and  supplying  the  missing 
hormone,  the  absence  of  which  may  have  produced 
the  entire  syndrome. 

From  this,  let  us  turn  to  the  consideration  of  the 
value  of  prescribing  fiver  extracts,  and  here  we  have 
to  accept  the  testimony  of  those  who  have  worked  on 
these  fines,  and  they  are  not  numerous,  as  certainly 
in  this  country  such  administration  has  not  been 
widely  supported. 

First  of  all  we  must  enumerate  the  actions  which 
liver  extracts  are  supposed  to  possess,  and  the  dis- 
orders in  which  they  have  been  employed.  Hepatic 
extract  has  been  employed  in  functional  disturbances 
of  the  liver,  in  those  cases  not  always  recognized  in 
textbooks  of  medicine,  but  which  are  very  well  known 


224   THE  ORGANS  OF  INTERNAL  SECRETION 

in  practice,  and  to  which  we  may  refer  as  "  congestion 
of  the  liver,"  "  hepatic  inactivity,"  or  "  hepatic  in- 
sufficiency." We  may  assume  that  in  such  cases,  and 
it  must  be  emphasized  that  we  are  referring  only  to 
functional  disturbances  of  this  organ,  for  some  reason 
the  secretion  of  the  hepatic  cells  (not  only  the  bile)  is 
deficient,  and  that  possibly  not  only  is  the  conversion 
of  the  products  of  digestion  incomplete,  but  that  the 
filter-function  of  this  organ  is  deficient.  It  used  to 
be  supposed  that  the  symptoms  of  a  ;'  congested 
fiver  "  owed  their  presence  to  bile  in  the  blood-stream; 
but  in  the  light  of  recent  work  it  is  much  more  probable 
that  other  and  more  complicated  processes  are  re- 
sponsible. 

Extracts  of  liver  have  been  prescribed  in  such  cases, 
much  along  the  lines  that  other  glandular  extracts 
have  been  prescribed  in  diseases  which  we  have  already 
discussed — that  is  to  say,  with  a  view  to  stimulating 
the  production  of  the  necessary  secretions,  and  to 
prevent  the  appearance  of  the  symptoms  which  we 
know  must  appear  if  the  absence  of  the  secretion 
concerned  is  allowed  to  persist.  But  this  is  only  one 
example  of  the  uses  to  which  these  extracts  have 
been  put.  Hepatic  cirrhosis  has  been  treated  by  the 
administration  of  liver  extract,  and,  more  especially 
in  the  atrophic  variety,  has  met  with  some  degree  of 
success. 

It  has  been  stated  that  such  administration  has  a 
marked  action  upon  nutrition,  and  assists  the  urinary 
excretion,  and  that  favourable  results  have  followed 


INTERNAL  SECRETIONS  OF  DIGESTION    225 

its  use  in  cirrhosis  of  the  liver,  as  well  as  in  functional 
congestion,  and  even  in  cancer.  It  is  only  rational 
to  assume  that,  provided  it  can  reach  its  goal  without 
being  destroyed  on  the  journey,  it  will  have  the 
power  either  to  replace  normal  secretion,  or  to  stimu- 
late that  part  of  the  secreting  mechanism  of  the  organ 
which  has  not  been  destroyed.  That  it  must  have 
some  action  in  replacing  the  deficiency  has  been 
shown  by  those  observers  who  have  demonstrated 
that  the  changes  in  excretion  alone  have  been  marked 
after  the  use  of  these  extracts.  Thus,  they  have 
shown  that  the  urea  index  is  markedly  increased,  as 
well  as  the  total  quantity  of  urine;  that  anasarca  has 
diminished,  and  that  the  tendency  to  hemorrhages, 
which  is  common  in  cirrhosis,  has  been  lessened. 

Again,  its  use  has  been  recommended  in  cases  of 
hepatic  diabetes,  and  where  the  diagnosis  has  been 
accurately  made  its  employment  should  do  good. 
Harrower  suggests  that  a  good  plan  to  adopt  when 
in  doubt  as  to  the  nature  of  glycosuria  is  to  com- 
mence treatment  with  pancreatic  preparations,  and  to 
administer  these  for  one  month,  and  then  if  no  favour- 
able result  be  obtained  to  try  liver  preparations.  He 
goes  on  to  emphasize  that  the  form  of  diabetes  associ- 
ated with  liver  disturbances  has  peculiar  character- 
istics, notably  that  the  glycosuria  occurs  at  definite 
times,  as  after  a  meal  or  in  the  evenings;  that  the 
major  symptoms  of  the  complaint,  such  as  thirst  and 
polyuria,  are  not  so  marked,  but  that  the  tendency 
to  infection  and  gangrene  is  well  seen.     From  this  he 

15 


226   THE  OEGANS  OF  INTEENAL  SECEETION 

infers  that  the  liver  is  failing  in  its  antibacterial 
powers.  It  is  in  these  cases,  according  to  this  author, 
that  hepatic  extracts  are  useful. 

It  will  be  quite  obvious  that  in  so  far  as  the  treat- 
ment of  diabetes  by  liver  extracts  is  concerned, 
diagnosis  is  the  essential  point;  and  that  whatever 
reliance  be  placed  upon  opo-therapy,  general  medicinal 
treatment  should  be  insisted  upon.  For,  as  we  have 
said  elsewhere,  the  more  we  learn  about  this  important 
subject,  the  more  are  we  impressed  with  the  fact  that 
a  regulated  diet  (in  order  to  spare,  so  far  as  is  possible, 
strain  upon  those  organs  concerned  with  sugar  meta- 
bolism) is  the  first  and  most  important  point. 

The  dose  of  liver  extracts  is  variable,  but  most 
authorities  are  agreed  that  it  should  be  administered 
in  generous  and  regular  doses.  It  is  said  that  extract 
of  this  organ,  administered  orally  or  per  rectum,  is 
practically  non-toxic,  and  that  it  may  be  given  in 
doses  ranging  from  15  or  20  grains  of  the  dried  extract 
every  hour,  and  increased  to  as  much  as  60  grains  three 
or  four  times  daily. 

A  few  words  about  bile  may  not  be  out  of  place  here. 
Bile  has  been  administered  to  patients  suffering  from 
"  sluggish  liver,"  and  with  excellent  results.  It  has 
been  shown  that  the  administration  of  even  small 
doses  of  bile  is  followed  by  a  marked  increase  in  the 
amount  of  bile  secreted;  and  it  is  along  these  lines 
that  treatment  by  biliary  extracts  has  been  followed. 
It  certainly  seems  more  rational  to  administer  the 
normal  stimulus  than  to  irritate  the  papilla  of  Vater 


INTEKNAL  SECRETIONS  OF  DIGESTION    227 

with  calomel.  For  relatively  small  doses  of  bile 
extract  are  cathartic — i.e.,  a  dose  of  10  grains — while 
5  grains  in  repeated  doses  has  a  laxative  effect.  The 
administration  of  the  biliary  extracts  is  followed  in 
many  cases  by  the  disappearance  of  the  signs  of 
intestinal  putrefaction,  such  as  meteorism  and  the 
passage  of  offensive  flatus,  and  by  the  re-establishment 
of  regular  and  formed  motions.  Bile,  although  not 
in  itself  an  antiseptic,  acts  in  the  intestine  as  such, 
for  it  prevents  stagnation  by  its  power  of  stimulating 
the  secretions  of  the  bowel. 

In  conclusion  we  must  refer  to  the  hormone  elabo- 
rated by  Zuelzer,  and  placed  upon  the  market  under 
the  name  of  "  Hormonal."  This  observer  examined 
gastric  mucous  membrane,  and  after  many  experiments 
succeeded  in  discovering  a  substance  which  proved  to 
possess  the  power  of  increasing  peristalsis.  Further, 
he  found  that  this  substance  was  elaborated  in  the 
stomach  and  small  bowel  during  digestion,  carried  in 
the  blood,  and  for  the  most  part  stored  in  the  spleen. 
As  a  result  of  experiments  it  was  found  that  this 
substance,  when  injected  into  the  blood,  produced 
a  marked  increase  in  peristalsis.  In  another  chapter 
we  deal  more  fully  with  this  hormone,  so  that  at  this 
place  we  will  content  ourselves  with  saying  that  the 
administration  of  this  substance  was  followed  by  cer- 
tain symptoms  of  an  undesirable  character,  and  that 
its  use  was  discontinued  in  favour  of  "  neo-lwrmonal," 
which  is  stated  to  be  free  from  the  objectionable 
features.     Neo-hormonal   is    usually   given    by   intra- 


228   THE  ORGANS  OF  INTERNAL  SECRETION 

muscular  injection,  but  it  has  recently  been  given 
by  the  mouth,  and  the  results  have  been  promising. 

It  is  probable  that  the  stomach  and  duodenum 
produce  a  substance  which  has  the  power  of  stimulating 
intestinal  movements,  and  that  this  hormone  is  largely 
responsible  for  the  regular  and  daily  evacuations  which 
are  characteristic  of  health.  If  further  experience 
shows  that  neo-hormonal  can  rectify  an  intestinal 
musculature  which  has  become  sluggish,  it  will  prove 
of  the  greatest  value  to  therapeutics. 

Among  the  abdominal  organs  which  have  been  said 
to  influence  digestion  is  the  spleen.  The  exact  func- 
tion of  this  organ  is  still  shrouded  in  mystery,  although 
certain  attributes  are  now  recognized.  That  it  is 
concerned  in  the  formation  of  certain  of  the  white 
corpuscles,  notably  the  lymphocytes,  is  now  admitted, 
while  it  is  believed  that  it  also  manufactures  large 
mononuclear  leucocytes.  It  is  said  to  be  the  filter 
which  removes  broken-down  corpuscles,  both  red  and 
white,  and  it  also  drains  the  blood-stream,  but  its 
haemopoietic  function  has  long  been  established. 

The  question  which  concerns  us  here  is,  How  is  the 
spleen  related  to  digestion  ?  It  would  appear  that  it 
exerts  a  definite  if  somewhat  remote  effect  upon 
digestion,  for  experiments  upon  animals  have  shown 
that  splenectomized  animals  do  not  obtain  nourish- 
ment from  their  food  in  the  same  way  that  normal 
animals  do.  In  other  words,  this  organ  enables  the 
main  digestive  glands  to  perform  their  work  more  ad  e- 
quately  than  is  possible  in  the  absence  of  the  spleen. 


INTERNAL  SECRETIONS  OF  DIGESTION    229 

It  has  been  assumed  from  the  results  of  these  and 
other  experiments  that,  while  the  spleen  is  not  an 
organ  that  is  essential  to  life,  its  purpose  is  partly  to 
regulate  the  blood-stream  and  its  contents,  and  partly 
to  influence  digestion,  although  our  knowledge  of  its 
exact  action  in  this  latter  respect  is  nil. 

An  inter-relation  is  suggested  by  the  fact  that  the 
spleen  has  been  found  to  be  enlarged  after  removal  of 
the  thyroid;  but  Biedl  says  that  this  cannot  be  regarded 
as  typical. 

Its  function  as  a  filter  is  clearer,  for  does  not  the 
spleen  enlarge  in  many  acute  infections,  notably 
enteric  ?  It  is  possible  that  it  is  concerned  in  prevent- 
ing the  products  of  intestinal  fermentation  from  re- 
maining in  the  blood-stream,  and  that  it  secretes  a 
chemical  which  is  destructive  to  micro-organisms. 
The  enlargement  which  is  so  commonly  seen  in  dis- 
ease would  then  be  accounted  for  by  a  hypertrophy 
in  response  to  a  sudden  demand  for  additional  defences 
against  infection. 

This,  of  course,  is  purely  speculative,  and  we  have, 
at  present,  no  evidence  in  support  of  this.  But  it  is 
hardly  conceivable  that  an  organ  of  this  size  can  be 
for  no  purpose,  beyond  the  contributory  hemopoietic 
function  which  it  shares  with  other  organs.  In  spite 
of  the  fact  that  splenectomy  is  not  followed  by  fatal 
results,  and  that  after  this  operation  other  glands 
take  on  the  known  functions  of  the  spleen,  it  seems 
highly  probable  that  the  future  will  disclose  some 
fresh  facts  about  the  splenic  function,  and  will  prove 


230   THE  OEGANS  OF  INTERNAL  SECRETION 

beyond  doubt  that  it  elaborates  a  hormone  which  may- 
be included  among  the  internal  secretions  of  digestion. 

Splenic  extract  has  been  prescribed  in  a  wide  variety 
of  cases.  Thus,  it  has  been  given  in  typhoid  with 
good  results;  in  splenomegaly,  in  malaria,  also  in 
anaemia,  and  in  morbid  states  associated  with  a  low 
blood-count.  Some  observers  speak  enthusiastically 
of  its  influence  in  reducing  the  size  of  an  enlarged 
spleen,  more  especially  in  what  we  may  speak  of  as 
"  idiopathic  "  splenomegaly. 

The  dose  of  splenic  substance  varies  widely  with 
different  authorities,  but  large  doses  of  the  fresh  sub- 
stance are  said  to  be  badly  tolerated.  The  dry  extracts 
may  be  given  in  doses  of  a  few  grains,  and  as  much 
as  15  grains  daily  are  usually  well  tolerated.  It  un- 
doubtedly finds  a  useful  field  of  activity  in  exhaustive 
maladies,  and  in  patients  showing  signs  of  a  diminished 
resistance  to  infection.  In  the  disease  just  referred 
to  it  may  confidently  be  administered,  with  the  object 
of  raising  the  resistance  to  the  invading  organism, 
assisting  metabolism,  and  thus  maintaining  the  strength 
of  the  patient. 

This,  then,  is  a  brief  survey  of  the  internal  secretions 
concerned  in  digestion,  and  of  their  relations  to  each 
other.  We  have  attempted  also  to  indicate  the  lines 
along  which  treatment  by  administration  of  the  ex- 
tracts of  these  organs  can  be  carried  out,  and  we  have 
tried  to  show  where  such  therapy  may  succeed.  As 
such  treatment  is  still  in  its  infancy,  and  as  there  are 


INTERNAL  SECRETIONS  OF  DIGESTION    231 

a  good  many  reasons  why  it  cannot  be  expected  to 
be  successful  in  every  case,  this  should  make  us  all 
the  more  careful  to  diagnose,  so  far  as  lies  in  our  power, 
the  exact  causation  of  every  case  which  we  treat  with 
organo-therapy;  and  we  should  remember  that,  while 
certain  of  these  preparations  are  toxic,  others  are  not 
so.  As  an  adjuvant  to  ordinary  methods,  the  extracts 
referred  to  in  this  chapter  should  be  found  very 
useful. 

References. 

1  Sweet  and  Pemberton,  Exp.  Observ.  on  "  Secretin,"  quoted 
in  Practitioner  ;  H.  R.  Harrower,  Practical  Hormone-Therapy. 

2  Harrower,  ibid.,  pp.  64-65. 

3  Langdon  Brown,  Practitioner,  vol.  xciv.,  No.  2,  p.  252. 

4  L.    Williams,   The   Therapeutic    Promise    of   the   Interna] 
Secretions,  Practitioner,  1911,  lxxxvii.  605. 


CHAPTER  XI 

THE  INTER-RELATIONSHIP  OF  THE  DUCTLESS 
GLANDS  AND  THE  NERVOUS  SYSTEM 

In  several  parts  of  this  book  reference  has  been  made 
to  the  mutual  relationship  existing  between  the  nervous 
system  and  the  internal  secretions.  The  sympathetic 
system  in  particular  shows  an  interaction  with  the 
endocrine  system,  both  morphologically  and  from 
the  physiological  standpoint.  In  this  chapter  it  is 
proposed  to  collect  the  facts  bearing  upon  the  inter- 
action of  the  nervous  system  and  the  ductless 
glands. 

We  will  commence  by  a  brief  description  of  the 
sympathetic  system,  in  the  hope  that  it  will  clarify  to 
some  extent  the  difficulties  which  beset  the  under- 
standing of  this  subject.  We  shall  then  discuss  in- 
dividual secretions  and  their  relation  to  nervous 
control,  and  conclude  with  a  summary.  In  the  next 
chapter  will  be  found  a  description  of  the  endocrine 
system  and  nervous  disorders,  more  particularly  those 
known  as  "  shell  shock,"  "  traumatic  neurasthenia," 
etc.,  for  they  form  examples  of  acute  disturbances 
associated  with  endocrine  manifestations. 

232 


HOEMONES  AND  THE  NEKVOUS  SYSTEM    233 

The  Sympathetic  System. 

In  his  work  on  "  The  Involuntary  Nervous  System,"1 
Gaskell  describes  the  sympathetic  nervous  system,  and 
makes  use  of  three  principles  which  deal  with  the  sub- 
divisions of  the  sympathetic,  their  relative  action,  and 
the  correlation  existing  between  the  endocrine  glands. 

The  first  principle  consists  in  the  recognition  of  two 
subdivisions  of  the  sympathetic  system:  (1)  The  auto- 
nomic, and  (2)  the  sympathetic  proper.  The  auto- 
nomic system  consists  of  that  portion  of  the  vegetative 
system  "  which  does  not  provide  centrifugal  rami 
communicantes  to  the  ganglia  which  lie  on  the  bodies 
of  the  spinal  column,  but  is  found  in  close  relation 
with  the  third,  seventh,  and  ninth  cranial  nerves,  and 
with  the  three  first  sacral  nerves."2  The  chain  of 
ganglia  receiving  the  rami  communicantes  from  the 
spinal  cord  and  the  visceral  ganglia  composes  the 
sympathetic  proper. 

The  next  point  of  importance  is  that  these  two 
portions,  both  of  which  innervate  the  viscera,  are 
antagonistic  to  each  other  in  regard  to  the  separate 
functions  of  those  organs. 

The  second  principle  concerns  the  selective  action  of 
the  endocrine  secretions  on  the  two  parts  of  the  vege- 
tative system.  It  has  been  shown  that  this  selective 
action  is  of  the  first  importance  in  the  regulation  of 
the  blood-supply  of  an  organ.  For  example,  to  take 
one  secretion  first,  about  which  there  is  no  doubt,  we 
know  that  adrenalin  acts  through  the  terminations  of 


234   THE  ORGANS  OF  INTERNAL  SECRETION 

the  true  sympathetic;  and  that  it  excites  the  secretions 
of  some  organs,  while  it  inhibits  others.  It  is  probable 
that  its  action  upon  metabolism  in  general  is  due  to  its 
stimulating  effects  upon  the  liver.  Experiments  have 
shown  that  stimulation  of  the  splanchnic  nerve  to  the 
liver  increases  glycogenosis,  and  that  this  only  occurs 
when  the  adrenals  are  intact.  The  work  of  Elliott  has 
shown  that  adrenalin  has  the  same  action  as  stimula- 
tion of  the  true  sympathetic.  As  an  instance  of  the 
inhibitory  action  of  adrenalin,  we  may  refer  to  its 
effect  upon  peristalsis,  which  is  exactly  analogous  to 
that  of  the  sympathetic. 

The  third  principle  is  the  recognition  of  the  special 
correlations  existing  between  these  glands.  There  is, 
as  we  have  seen  in  other  parts  of  this  book,  a  mutual 
action  between  some  secretions,  and  an  antagonistic 
action  between  others.  One  secretion  may  stimulate 
into  activity  the  product  of  another  gland,  in  this 
sense  a  "true  hormone";  a  second,  however,  may 
inhibit  the  secretion  of  another  member  of  the  endo- 
crine group.  The  adrenal  secretion  has  a  stimulating 
action  upon  the  pituitary  and  upon  the  thyroid;  either 
produces  a  similar  action  upon  the  adrenal.  All  three 
can  inhibit  the  secretion  of  the  pancreas,  and  perhaps 
also  that  of  the  parathyroid  and  thymus  glands. 

Other  assisting  and  antagonizing  actions  at  once 
occur  to  the  reader;  and  in  Chapter  I.  will  be  found 
other  instances.  It  is  possible,  moreover,  that  the 
antagonism  existing  between  the  two  parts  of  the 
vegetative  nervous  system  may  depend  on  the  various 


HOKMONES  AND  THE  NEKVOUS  SYSTEM    235 

actions  of  the  endocrine  glands.  It  is  probable,  also, 
that  the  tone  of  the  visceral  nervous  system  is  main- 
tained and  influenced  by  the  secretions  of  the  endo- 
crine glands.  It  will  repay  us,  therefore,  to  familiarize 
ourselves  with  what  is  now  known  about  the  nervous 
supply  of  the  visceral  organs  and  the  sympathetic 
system  as  a  whole,  and  to  try  and  understand  how  this 
is  linked  up,  and  its  action  modified  by  the  internal 
secretions. 

Gaskell,  whose  work  on  the  involuntary  nervous 
system  has  thrown  so  much  light  upon  this  subject, 
summarizes  the  divisions  and  actions  of  the  sympa- 
thetic system  in  the  last  chapter  of  his  book.*  He 
divides  the  unstriped  muscles  of  the  vertebrates  into 
certain  groups,  classified  according  to  their  innervation 
and  their  response  to  "  certain  substances  formed 
naturally  in  the  body."  There  are  six  groups  in  all: 
five  of  these  respond  to  very  small  quantities  of 
adrenalin,  while  the  sixth  (the  musculature  of  the 
endoderm)  contracts  in  the  presence  of  a  small  quantity 
of  acetyl- choline.  "  The  striking  action  of  these  two 
substances,  adrenaline  and  acetyl- choline,  is  correlated 
with  the  differences  in  the  innervation  of  these  two 
groups  of  muscles,  "f 

In  explaining  the  action  of  these  two  groups  from 
the  embryological  standpoint,  Gaskell  says  that 
investigations   show   the   nerve    cells   of    both   were 

*  "  The  Involuntary  Nervous  System,"  Chapter  XII.,  p.  150 
et  seq.     Longmans,  Green  and  Co.,  1920. 
f  Ibid.,  p.  150. 


236  THE  ORGANS  OF  INTERNAL  SECRETION 

originally  in  the  central  nervous  system,  but  that,  in 
travelling  out  from  it,  the  sympathetic  cells  have  been 
accompanied  by  adrenalin- containing  cells,  and  that 
these  cells  form  the  chromaffin  system.  Cells  of  this 
nature  are  seen  in  the  leeches,  and  Gaskell  considered 
that  they  form  the  origin  of  both  the  sympathetic  and 
chromaffin  cells  of  the  vertebrate. 

These  nerve  cells,  originating  in  the  central  nervous 
system,  include  inhibitory  and  motor  cells  in  both 
nervous  systems  (sympathetic  and  enteral),  the  in- 
hibitory cells  of  one  system  travelling  with  the  motor 
cells  of  the  other,  thus  establishing  the  antagonism, 
exemplified  by  such  a  mechanism  as  the  sphincter. 

Turning  now  to  the  relation  between  the  nervous 
and  humoral  control  of  metabolism,  we  have  already 
referred  to  the  work  of  Eppinger  and  Hess.*  These 
writers  consider  that  two  groups  of  symptoms  may 
exist,  the  one  dependent  upon  the  cranio-sacral 
system  and  called  vago-tonia,  the  other  characterized 
by  over-action  of  the  sympathetic  part  of  the  vegetative 
nervous  system,  and  called  sympathetico-tonia,  or 
sympathotonia. 

It  has  been  noted  that  disturbances  of  the  autonomic 
system  are  associated  with  disorders  such  as  those  seen 
in  the  lymphatic  diathesis,  and  in  which  the  thyroid, 
thymus,  and  other  of  the  ductless  glands,  are  believed 
to  be  implicated.  On  the  other  hand,  the  sympatho- 
tonic  symptoms  are  those  seen  in  hyperthyroidism — 
hyperthermia,  restlessness,  tachycardia,  and  atony  of 
*  Chapter  HI.,  p.  63. 


HORMONES  AND  THE  NERVOUS  SYSTEM    237 

the  stomach  and  intestines.  If,  then,  this  is  the  under- 
lying pathology  of  those  cases  known  as  Graves'  disease, 
it  would  be  interesting  if  we  could  take  the  investiga- 
tion one  step  farther  and  find  out  whether  this  atony, 
which  is  a  constant  feature  of  this  type  of  case,  is 
dependent  upon  over-stimulation  of  the  enteral  sym- 
pathetic system  by  a  chemical  manufactured  in  the 
body,  either  one  belonging  to  the  normal  endocrine 
group  or  one  resulting,  e.g.,  from  the  products  of 
intestinal  digestion.  If  we  could  say,  as  Gautrelet  did, 
that  the  action  of  tissue  extracts  is  due  to  choline,  we 
might  have  advanced  a  step;  for  we  could  believe,  with 
him,  that  the  "  choline  glands  "  were  antagonistic  to 
the  "  adrenalin  glands."  But  this  appears  not  to  be 
so.  Swale  Vincent  says,  "  Even  if  the  action  of  tissue 
extracts  were  in  reality  due  to  choline,  there  would  be 
no  grounds  for  such  an  assumption  as  is  here  put  for- 
ward. The  theory  that  the  normal  blood-pressure  is 
maintained  by  a  series  of  antagonistic  chemical 
messages  arriving  from  the  different  glands  and  tissues 
of  the  body  has  been  put  forward  previously  in  different 
forms,  but  there  is  no  experimental  evidence  to  sup- 
port it."3 

It  does  appear,  however,  that  not  only  the  vegetative 
nervous  system  is  controlled  and  affected  by  endocrine 
action,  but  also  the  entire  nervous  system.  The 
changes  seen  after  parathyroidectomy  are  certainly 
suggestive  of  a  widespread  involvement  of  the  nervous 
system,  and  the  clinical  evidence  of  the  psycho- 
physical condition  of   cretins  before  and  after  they 


238  THE  OEGANS  OF  INTERNAL  SECRETION 

have  been  furnished  with  thyroid  extract  may  well 
support  this  belief.  One  observer  has  put  forward 
the  theory  that  the  neuroglia  may  be  included  among 
the  hormone-producing  glands,  and  that  the  secretion 
of  this  tissue  has  widespread  influences  upon  the 
sensitivity  of  the  nervous  system. 

The  clearest  relation  which  has  yet  been  established 
between  the  nervous  and  the  humoral  control  is  that 
of  the  true  sympathetic  and  of  adrenalin.  We  know 
that  the  action  of  adrenalin  is  identical  with  that  pro- 
duced by  stimulation  of  the  sympathetic,  and  the 
work  of  Gaskell  has  suggested  how  this  has  been 
brought  about.  He  pointed  out  that  in  segmented 
annelids  certain  nerve-cells  in  the  central  nervous 
system  contain  adrenalin,  and  he  says  that  in  this 
class  of  the  vertebrates  "  we  are  watching  the  genesis 
of  the  sympathetic  nervous  system." 

The  knowledge  which  the  future  holds  for  the 
student  of  the  internal  secretions  will  be  largely  built 
up  upon  investigations  into  the  action  of  the  vegetative 
nervous  system. 

The  Relation  of  Hormones  to  Nervous  Control. 

We  have  seen  that  embryology  shows  the  intimate 
relation  existing  between  the  chromaffin  tissue  and 
the  nervous  system,  and  that  physiology  proves  their 
similarity  in  action.  In  this  section  we  shall  draw 
attention  to  the  mutual  relations  of  various  hormones 
and  the  nervous  system. 


HORMONES  AND  THE  NERVOUS  SYSTEM    239 

Asher  and  von  Rodt  showed  the  production  of  the 
internal  secretion  of  the  thyroid  to  be  under  the  control 
of  the  nervous  system.  From  the  other  view-point 
the  action  of  the  thyroid  secretion  upon  the  central 
nervous  system  is  very  striking,  and  is  well  shown  in 
typical  instances  of  hyper-  and  hypo-thyroidism.  The 
response  to  stimuli  in  these  two  conditions  is  widely 
different. 

The  effect  upon  metabolism  of  thyroidectomy  is 
interesting.  Large  amounts  of  sugar  may  be  given 
after  removal  of  the  thyroid  without  the  production  of 
glycosuria.  This  means  that  the  sugar  is  stored  and 
not  mobilized.  Adrenalin,  as  we  have  already  seen, 
has  an  action  in  the  mobilizing  of  sugar,  and  it  is 
possible  that  the  loss  of  the  thyroid  secretion  decreases 
the  action  of  the  adrenalin  in  producing  glycosuria. 
Both  the  thyroid  and  the  adrenals  probably  act  upon 
the  same  mechanism,  the  thyroid  secretion  producing 
its  action  by  stimulating  the  terminations  of  the 
sympathetic  in  the  liver  (Paton). 

If  adrenalin  be  instilled  into  the  conjunctival  sac 
in  patients  suffering  from  hyperthyroidism,  dilatation 
of  the  pupil  is  produced,  which  is  an  example  of  the 
action  of  adrenalin  where  the  thyroid  is  in  excess. 
The  thyroid  exerts  its  influence  upon  carbohydrate 
metabolism  mainly  through  nervous  channels.  It  is 
probable  that  the  same  mechanism  is  involved  when 
protein  metabolism  is  concerned,  because,  as  Paton 
says,  the  close  relation  existing  between  sugar  forma- 
tion and  protein  metabolism  is  now  recognized.     The 


240  THE  ORGANS  OF  INTERNAL  SECRETION 

work  of  Mansfeld,  which  showed  that  the  increased 
nitrogen  output  which  usually  follows  the  deprivation 
of  oxygen  does  not  take  place  after  thyroidectomy, 
"  shows  how  close  the  association  of  the  thyroid  is  with 
protein  catabolism."*  This  association  appears  to  be 
brought  about  by  the  influence  of  the  thyroid  upon  the 
liver.  In  like  manner  the  evidence  of  physiological 
experiments  is  in  favour  of  the  view  that  adrenalin 
acts  upon  metabolism  through  the  nerve  terminations 
in  the  liver.  The  antagonistic  action  of  ergotoxin  and 
adrenalin  in  this  relation  suggests  that  the  action  is 
on  nerve- endings. 

The  nerve  and  endocrine  relations  with  reference  to 
the  parathyroids  have  already  been  discussed.  The 
thymus  and  parathyroids  are  similar  in  their  action 
upon  the  nervous  system.  Both  exercise  a  depressing 
effect,  which  has  been  attributed  to  the  metabolic 
changes,  more  particularly  with  regard  to  diminution 
in  the  calcium  content.  Paton  rejects  both  this  ex- 
planation and  that  of  an  acid  intoxication  which  has 
been  put  forward  to  explain  the  symptoms  of  tetany: 
the  former  because,  in  dogs  dying  of  tetany,  the  brains 
have  been  found  to  contain  a  slightly  greater,  not  less, 
proportion  of  calcium;  the  latter  because,  experi- 
mentally, the  amount  of  ammonia  required  to  produce 
symptoms  of  acidosis  is  very  large. 

The  action  of  the  thymus  and  the  parathyroids  is 
probably  directly  upon  the  spinal  synapses.     This  is 


*  .. 


The  Regulators  of  Metabolism,"  p.  199. 


HORMONES  AND  THE  NERVOUS  SYSTEM    241 

of  a  depressing  nature,  and   is  the  opposite  of  that 
exercised  by  the  thyroid  gland. 

Pituitary  extract  is  analogous  to  adrenalin  in  its 
action  upon  the  metabolism  of  carbohydrates,  and 
probably  also  by  means  of  nerve- endings  in  the  liver- 
The  question  whether  it  acts  upon  muscle  fibre,  upon 
the  neuromuscular  function,  or  upon  the  nerve- endings, 
has  not  been  settled. 

The  gonads  must  be  studied  from  the  two  stand- 
points we  adopted  in  Chapter  IX. — namely,  their 
effects  upon  growth  and  metabolism  and  their  effects 
in  producing  the  phenomena  of  sex.  As  regards  the 
first,  little  is  known  as  to  how  the  effects  associated 
with  the  presence  or  absence  of  the  gonads  in  both 
sexes  are  brought  about.  Certainly  it  cannot  be  said 
that  there  is  conclusive  evidence  that  it  is  by  direct 
action  upon  the  nervous  system,  although  it  may  be 
that  these  effects  are  brought  about  by  action  upon 
the  vasomotor  mechanism.  The  influence  which  the 
internal  secretion  of  the  gonads  exerts  upon  the 
sexual  characteristics  is  undoubtedly  by  means  of 
the  nervous  system;  for  the  study  of  animals  has 
shown  beyond  question  that  it  is  by  means  of  nervous 
reflexes  that  these  characteristics  are  brought  about.* 
The  pancreas  exerts  an  inhibitory  action  upon  the 
adrenal  secretion,  so  far  as  the  mobilization  of  sugar 
is  concerned.  Paton  thinks  it  is  probable  that  the 
pancreatic  secretion  acts  upon  the  same  structures  as 

*  See  Chapter  IX.,  p.  202,  for  an  account  of  the  experiments 
of  Steinach. 

16 


242  THE  OEGANS  OF  INTERNAL  SECRETION 

the  adrenals  and  the  thyroid  in  this  relation,  but  in  the 
opposite  direction,  inhibiting  instead  of  facilitating. 
We  thus  have  a  common  neural  basis,  stimulated  by 
one  set  of  secretions  and  inhibited  by  another.  Such 
a  balance  is  probably  often  in  action  in  the  course  of 
metabolism,  or  some  modification  of  this  mechanism 
is  made  use  of  to  bring  about  the  complicated  metabolic 
exchanges. 

Summary. 

1.  The  vegetative  nervous  system  is  composed  of 
two  parts,  the  autonomic  and  the  sympathetic. 

2.  These  two  parts  are  antagonistic  to  each  other  in 
so  far  as  the  functions  of  the  organs  are  concerned. 
This  is  shown  by  their  reaction  to  drugs — e.g.,  pilo- 
carpine stimulating  the  autonomic  and  adrenalin  the 
sympathetic. 

3.  The  various  internal  secretions  have  a  selective 
action  upon  the  two  parts  of  the  vegetative  system: 
the  pituitary  secretion  stimulates  the  autonomic, 
adrenalin  the  sympathetic. 

4.  There  is  reason  to  believe  that  the  chromaffin 
tissue  has  been  evolved  from  the  central  nervous 
system  by  means  of  cells  which  have  travelled  out- 
wards carrying  adrenalin  with  them.  This  is  additional 
evidence  of  the  intimate  relationship  which  exists 
between  the  involuntary  nervous  system  and  the 
internal  secretions. 

5.  The  complex  activities  of  the  body,  both  metabolic 
and  vasomotor,  are  brought  about  both  by  means  of 


HOEMONES  AND  THE  NEEVOUS  SYSTEM    243 

hormones  and  by  nervous  influences  activating  these 
secretions.  In  many  instances  there  is  experimental 
evidence  to  show  that  the  chemical  stimulus  is  the 
more  important,  and  that  it  plays  a  larger  part  in  the 
regulation  of  metabolism  than  does  the  nervous. 

6.  The  development  of  a  nervous  system  is  a  com- 
paratively late  event,  stimuli  being  primarily  of  a 
chemical  nature.  This  would  suggest  that  the  chemical 
is  the  dominant  factor. 

7.  The  chief  if  not  all  the  functions,  in  connection 
with  metabolism,  are  regulated  by  two  sets  of  im- 
pulses, a  stimulatory  and  an  inhibitory.  The  auto- 
nomic and  the  sympathetic  balance  each  other  from  the 
nervous  aspect,  while  the  chemical  is  served  by  two 
secretions  having  opposing  actions  so  far  as  a  par- 
ticular function  is  concerned. 


References. 

1  W.  H.  Gaskell,  The  Involuntary  Nervous  System.     (1920.) 

2  R.  G.  Rows  and  David  Orr,  Functional  Mental  Illnesses. 

3  Swale  Vincent,  Internal  Secretion  and  the  Ductless  Glands. 


CHAPTER  XII 

THE    ENDOCRINE    GLANDS   AND    NERVOUS 
DISORDERS 

Introduction. 

Since  the  first  edition  of  this  book  was  published, 
considerable  work  has  been  done  on  the  relation 
between  the  various  endocrine  glands  and  disorders 
of  the  nervous  system.  The  interest  in  this  work  has 
been  accentuated  by  the  numerous  and  striking  cases 
of  functional  disease  attributable  to  the  war,  many 
of  which  present  features  unlike  anything  previously 
met  with. 

In  this  chapter  the  author  proposes  to  discuss  the 
more  recent  work  which  has  been  done  on  the  com- 
plicated physico- psychical  basis  of  these  disorders; 
and  to  consider  at  some  length  the  part  played  by  the 
internal  secretions. 

In  a  certain  proportion  of  the  functional  nervous 
disorders — those,  to  wit,  which  have  been  christened 
"  shell-shock,"  "  shell- concussion,"  "  traumatic  neuras- 
thenia," etc. — there  are,  very  frequently,  ample  evi- 
dences that  somewhere  in  the  chain  of  cause  and 
effect  there  enters  the  element  of  the  internal  secre- 

244 


THE  BNDOCEINE  GLANDS  245 

tions.  In  any  large  number  of  such  cases,  particularly 
if  examined  at  an  early  stage,  a  certain  proportion 
will  be  found  to  show  symptoms  which  lead  us  to 
suspect  undue  stimulation  of  one  of  these  vital 
chemicals,  the  internal  secretions.  Others,  cases  of 
longer  duration,  will  develope  in  the  course  of  weeks 
or  months  such  definite  signs  as  tachycardia,  undue 
sweating,  enlargement  of  the  thyroid,  fine  tremor  and 
loss  of  flesh  with  asthenia.  The  sympathetico-tonic 
picture  thus  displayed  is  very  striking;*  and  it  is  often 
enough  encountered  among  the  war  psycho-neuroses 
to  make  the  neurologist  on  the  lookout  for  such 
indications.  Among  a  large  number  of  functional 
neurological  patients  which  the  present  writer  has 
had  the  opportunity  of  observing,  both  in  France  and 
in  this  country,  there  were  many  who  displayed  one 
or  more  of  the  symptoms  named  above. 

When  the  effect  of  adrenal  stimulation  which  follows 
emotional  shock  is  taken  into  consideration,  it  is  only 
to  be  expected  that  such  symptoms  should  be  ob- 
served. Cannon,  in  his  classic  work  on  this  subject, 
showed  that  the  role  of  the  adrenals  was  of  prime 
importance  in  maintaining  nerve- tone;  and,  further, 
that  one  of  the  effects  of  adrenal  stimulation  was 
increased  action  of  the  heart,  vasomotor  excitability, 
and  other  symptoms,  which  are  also  seen  after  psychical 
stimulation.  We  shall  refer  later  in  greater  detail  to 
the  bearing  this  has  upon  our  present  study. 

*  See  Chapter  III.,  p.  63,  for  reference  to  the  type  of  case 
which  Eppinger  and  Hess  have  thus  described. 


246   THE  ORGANS  OF  INTERNAL  SECRETION 

If  the  adrenals,  to  take  one  factor  in  the  endocrine 
circle,  suffer  undue  stimulation,  we  now  know  that 
the  changes  resulting  are  not  due  solely  to  the  secretion 
of  those  glands,  but  that  others  are  in  turn  affected. 
For  instance,  it  has  been  shown  by  Osokin*  that  the 
adrenals  have  a  definite  effect  upon  the  thyroid:  for 
this  observer  produced  marked  histological  changes 
in  the  cells  of  this  gland  by  repeated  injections  of 
adrenin.  Moreover,  stimulation  of  the  splanchnics 
appears  to  produce  increased  thyroid  action. 

Here,  then,  we  arrive  at  a  further  stage  in  our 
initial  inquiry.  Presuming,  in  a  case  of  war-shock 
such  as  we  have  just  referred  to,  the  emotion  is  the 
initial  cause,  this  will  produce  an  increased  secretion 
of  adrenalin,  which  will  account  for  the  immediate 
symptoms,  such  as  are  seen  at  the  commencement  of 
the  disorder;  while  those  patients  who  show  these 
symptoms,  together  with  an  enlargement  of  the 
thyroid,  may  be  regarded  as  suffering  from  hyper- 
adrenahsm,  which,  in  turn,  has  reacted  upon  the 
thyroid,  producing  an  enlargement  of  this  organ. 
Such  an  hypertrophy  may  be  regarded  as  analogous 
to  that  produced  by  Osokin  in  his  experimental 
injections. 

It  will  be  noticed  that  we  have  assumed  a  psychical 
origin  in  such  a  case.  This  is  warranted  when  we 
consider — 

(i.)  That  Cannon   showed    that    purely  sensory 
stimuli  could  stimulate  glandular  secretion. 

*  Russk,  Cratch,  1U15,  xiv.  300  (quoted  from  Swale  Vincent). 


THE  ENDOCRINE  GLANDS  247 

(ii.)  That  in  the  majority  of  war  neuroses  the 
psychical  element  has  been  abundantly  proved 
to  play  a  most  important  part. 

To  obtain  a  clear  understanding  of  the  problems  of 
the  psycho-neuroses,  we  must  remember  that  the 
evidence  produced  by  Cannon  is  of  the  greatest  im- 
portance in  explaining  the  mechanism  of  these  dis- 
orders. For  he  showed  not  only  that  nerve-tone  was 
dependent  upon  the  regular  secretion  of  the  adrenals, 
but  that  the  latter  secretion  was  largely  determined 
by  the  mental  content. 

Before  discussing  the  physiological  facts  which 
recent  work  has  placed  at  the  disposal  of  the  neuro- 
logist, it  may  be  as  well  to  glance  at  the  psychological 
factors  which  underlie  so  many  of  these  nervous 
disturbances. 

The  Psycho-Neuroses. 

In  considering  these  neuroses  with  reference  to  the 
internal  secretions,  we  are  faced  with  an  initial  diffi- 
culty— namely,  the  ambiguity  in  the  meaning  of  the 
term  neurasthenia.  Neurasthenia  may  be  regarded 
as  a  nervous  exhaustion  in  the  sense  its  originator 
used  the  word:  for  Beard,  when  he  referred  to  neuras- 
thenia, considered  that  its  whole  origin  was  in  a 
lowering  of  the  nervous  potential,  and  in  his  conception 
he  included  the  mental  exhaustion  which  Janet  sub- 
sequently so  clearly  denned  under  the  term  "  psych- 
asthenia."     Or,  again,  neurasthenia  is  sometimes  used 


248   THE  ORGANS  OF  INTERNAL  SECRETION 

to  denote  every  symptom  which  is  ever  encountered 
in  the  psycho- neuroses.  Physical  exhaustion,  "  irrit- 
able weakness,"  gastro-intestinal  disturbances,  mental 
abnormalities  (including  the  manifestations  popularly 
known  as  hysteria),  phobias,  obsessions,  tics,  tremors, 
etc.,  are  all  included  under  this  term  by  some  writers. 
It  will  be  better,  perhaps,  not  to  attempt  at  present 
any  decision  between  the  different  meanings  of  the 
term  neurasthenia,  but  to  let  the  meaning  clear  itself 
in  the  course  of  our  description  of  the  relation  which 
the  endocrine  glands  bear  to  functional  nervous 
diseases.  We  commence,  therefore,  by  a  short  survey 
of  the  psycho- neuroses  in  general;  this  will  lead  us  to 
a  definite  idea  of  the  syndrome  of  symptoms  included 
under  the  various  terms:  we  can  then  consider  the 
relation  each  disease  bears  to  the  endocrine  glands, 
so  far  as  we  are  able  to  discriminate  between  them. 

(a)  Historical. 

Until  the  latter  part  of  the  nineteenth  century 
functional  nervous  disorders  remained,  for  practical 
purposes,  undifferentiated.  The  popular  conception 
of  "  nerves,"  which  remains  undefined  and  undefmable 
to  the  present  day,  held  undisputed  sway.  This  may 
fairly  be  said  to  summarize  the  existing  state  of 
neurology  until  Beard,  about  the  middle  of  the  nine- 
teenth century,  introduced  the  term  "neurasthenia." 
Beard  included  in  this  term,  as  we  have  already  said, 
all  those  variegated  symptoms  which  he  regarded  as 
due,    directly   or    indirectly,   to   an   organic   nervous 


THE  ENDOCRINE  GLANDS  249 

exhaustion.*     At  that  time  no  psychogenic  conception 
had  arisen  to  account  for  any  or  all  these  manifestations. 

This  view  was  largely  held,  especially  in  America, 
until  Charcot  put  forward  the  doctrine  that  hysteria 
(to  take  one  more  or  less  clear-cut  clinical  picture) 
was  dependent  upon  idiogenic  causes.  He  showed 
clearly  that  the  individual  manifestations  of  this  dis- 
order owed  their  origin  to  mental  workings.  Charcot's 
outlook  may  be  said  to  have  revolutionized  the 
views  held  at  that  time  in  regard  to  functional 
neuroses. 

The  idiogenic  conception  of  hysteria  was  enlarged 
upon  by  Mobius,  whose  view  was  that  the  manifesta- 
tions of  hysteria  were  due  to  "  representations." 
This  brings  us  to  the  work  of  Janet,  whose  writings 
(from  1889  to  1903)  have  given  us  three  clear-cut 
pictures  into  which  we  can  fit  the  many  mental  and 
physical  abnormalities  which  were  formally  dumped 
together  under  the  generic  name  of  "  nervous 
exhaustion." 

Janet  divides  the  symptoms  and  signs  of  the  psycho- 
neuroses  into  three  groups,  which  he  calls  hysteria, 
psychasthenia,  and  neurasthenia.  For  hint,  hysteria 
represents  a  typical  mental  disintegration  (dedouble- 
ment)  taking  the  form  of  what  he  calls  a  "  molar 
dissociation.  "| 

*  See  articles  by  author,  Practitioner,  April,  1913,  and  August, 
1915,  for  a  description  of  this  conception. 

|  By  "  molar  dissociation "  Janet  means  a  dissociation  en 
masse,  a  splitting  of  the  mental  processes,  so  that  two  separate 
and  uncomiected  streams  exist  in  the  mind.     By  this  concep- 


250   THE  OEGANS  OF  INTEENAL  SECEETION 

(b)  Janet's  Conceptions. 

In  his  conception  of  hysteria,  Janet  includes  such 
symptoms  as  anaesthesias,  amnesias,  somnambulisms, 
"attacks,"  etc.;  and  these  he  explains  as  being  due 
to  a  splitting  of  the  mental  processes. 

By  psychasthenia,  Janet  indicates  cases  of  psychical 
instability  characterized  by  a  formidable  list  of 
symptoms,  classified  by  this  author  into  groups. 
These  groups  comprise  obsessive  ideas  and  impulses, 
"  forced  agitations  "  (including  the  anxiety  neurosis), 
feelings  of  incompleteness,  and  insufficiencies,  whether 
of  psychological  or  physiological  causation.  These  he 
ascribes  to  a  loosening  of  the  elements  which  go  to 
make  up  the  entire  personality,  and  not  to  a  complete 
cleavage  as  occurs  in  hysteria. 

Neurasthenia  is  also  retained  by  Janet,  but  used 
to  denote  those  cases  characterized  primarily  by 
physiological  exhaustion  (gastro-intestinal  atony,  un- 
due fatigability,  etc.). 


tion,  he  accounts  for  the  anaesthesias,  amnesias,  paralyses  and 
contractions,  etc.,  so  commonly  encountered  in  this  complaint. 
Such  a  view  goes  far  towards  explaining  the  apparently  anoma- 
lous character  of  functional  disorders — e.g.,  a  functional  para- 
plegic who  can  "  walk  in  his  sleep,"  or  the  deaf-mute  who 
"  blinks  "  at  a  loud  noise,  thus  showing  that  some  appreciation 
of  the  sound  has  been  conveyed  to  his  mind. 

In  similar  manner,  he  accounts  for  the  symptoms  of  psych- 
asthenia, attributing  them  to  a  certain  dissociation  which  he 
calls  "  molecular " — i.e.,  not  en  masse  (loosening  of  the 
personality,  not  an  entire  cleavage). 


THE  ENDOCEINE  GLANDS  251 

Since  Janet's  time,  his  theories  have  been  expanded 
and  adapted,  but,  in  particular,  his  conception  of  the 
causes  of  these  dissociations  has  been  replaced  to  a 
large  extent  by  the  work  of  Freud,  Jung,  Adler, 
and  others.  These  authors  have  evolved  elaborate 
mechanisms  to  explain  the  "  dissociations  '  which 
are  presumed  to  be  at  the  basis  of  the  psycho- 
neuroses. 

Ketaining  for  the  moment  the  conception  of  dis- 
sociation of  mental  processes,  we  naturally  ask  for 
some  more  definite  reason  for  this  dissociation  than 
the  "  sticking  together  "  hypothesis  given  by  Janet. 
Freud  and  his  followers  offer  reasons  for  such  dis- 
sociations; and  these  are  to  be  found  in  the  existence 
of  complexes,  conflicts,  indirect  manifestations  of 
repressions,  etc.  Such  mental  occurrences  as  these 
are  the  explanations  of  why  dissociation  occurs;  and 
afford  a  useful  guide  in  endeavouring  to  understand 
the  mental  mechanisms  at  the  basis  of  the  psycho- 
neuroses. 

(c)  Nomenclature. 

It  is  hoped  that  this  digression  will  help  us  to  under- 
stand some  of  the  difficulties  which  face  us  in  en- 
deavouring to  trace  the  various  links  in  the  chain  of 
cause  and  effect  which  constitute  the  typical  case  of 
functional  nervous  disease.  It  has  been  inserted  here 
in  an  endeavour  to  crystallize  our  ideas  as  to  these 
disorders ;  so  that  in  any  further  reference  to  the  sub- 
divisions of  the  psycho-neuroses  in  this  chapter,  the 


252   THE  ORGANS  OF  INTERNAL  SECRETION 

reader  may  grasp  clearly  to  what  particular  group  of 
symptoms  we  are  referring. 

We  are  bound  to  admit  that  in  all  these  patients  the 
physical  and  psychical  elements  are  more  inextricably 
blended,  and  less  easily  recognizable  than  in  any 
ordinary  disease.  Any  classification,  such  as  we  have 
just  recounted,  must  perforce  be  limited  in  its  utility, 
for  it  is  not,  and  probably  never  will  be,  possible 
absolutely  and  arbitrarily  to  make  any  complete  and 
final  classification  of  the  psycho- neuroses,  for  the 
reason  that  it  is  equally  impossible  to  divide  indi- 
viduals into  absolutely  clear-cut  temperaments.  The 
most  we  can  do  is  to  lay  down  rough  boundaries, 
marking  off  one  type — comprising  a  more  or  less 
constant  group  of  symptoms — from  others. 

By  hysteria,  then,  we  mean  that  group  of  cases 
exhibiting  the  features  outlined  by  Janet.  It  is 
characterized  by  the  symptoms  we  have  enumerated.* 
By  psychasthenia,  we  refer  to  cases  characterized  by 
phobias,  hesitations,  doubts,  anxieties,  etc.;  while  the 
term  neurasthenia  will  be  kept  for  the  cases  showing 
a  preponderance  of  symptoms  referable  to  physical 
exhaustion — e.g.,  fatigability,  indigestion,  disturbances 
of  excretion.  This  rough-hewn  classification  will,  it 
is  hoped,  serve  to  keep  any  subsequent  remarks  about 
the  internal  secretions  and  their  relations  to  these 
disorders  more  or  less  clear. 

*  The  cases  referred  to  by  Freud  as  "  conversion  "  hysteria, 
form  a  large  part  of  the  war  cases  of  hysteria.  By  this  term 
is  meant  those  cases  in  which  mental  energy  is  converted  from 
normal  to  abnormal  somatic  manifestations. 


THE  ENDOCBINB  GLANDS  253 

(d)  War  Nomenclature. 

Since  the  war  began,  many  new  terms  have  come 
into  more  or  less  general  use  to  describe  the  functional 
nervous  disturbances  arising  from  the  incidentals  of 
active  service  Of  these  probably  "  shell-shock  "  is 
the  most  commonly  in  use.  What  is  meant  by  this 
term  it  is  not  always  easy  to  say.  Presumably  its 
use  in  the  popular  mind  is  to  include  any  functional 
nervous  disturbance  occurring  under  shell-fire  without 
any  external  injury.  Such  use  obviously  would 
include  any  condition  from  what  is  known  in  the 
vernacular  to  "  having  the  wind  up,"  to  a  serious 
lesion  such  as  intra- dural  haemorrhage.  Its  scientific 
use  is  hardly  more  satisfactory.  It  definitely  includes 
a  condition  of  concussion,  either  cerebral  or  spinal; 
all  functional  nervous  disorders ;  and  it  has  even  been 
used  to  denote  a  psycho- neurosis  arising  on  home 
service ! 

To  prevent  needless  misconception  this  term  should 
be  kept  for  "  the  condition  which  follows  exposure  to 
the  forces  generated  by  the  explosion  of  powerful 
shells  in  the  absence  of  any  visible  injury  to  the  head 
or  spine.  In  all  cases  there  is  an  organic  basis,  which 
consists  of  the  more  or  less  evanescent  changes  in 
the  central  nervous  system  resulting  from  the  con- 
cussion caused  by  aerial  compression,  to  which  is  often 
added  concussion  of  the  head  or  spine  caused  by  the 
sandbags  of  a  falling  parapet,  or  by  the  patient  being 
blown  into  the  air  and  falling  heavily  on  to  his  head 


254   THE  ORGANS  OF  INTERNAL  SECRETION 

or  back.     On  this  organic  basis  hysterical  or  psych- 
asthenic symptoms  are  often  superposed."* 

So  much  for  shell-shock.  Where  a  history  of  definite 
trauma  is  obtainable,  it  will  be  found  that  the  term 
"  shell- concussion  "  is  convenient  and  accurate.  In 
those  cases  where  the  explosion  has  occurred  in  a 
confined  space,  the  patient  is  liable  to  be  rendered 
unconscious  by  the  effects  of  carbon  monoxide  poison- 
ing, as  Mott  has  pointed  out. 

In  many,  if  not  the  majority,  of  cases  of  functional 
disorder  arising  in  the  firing- zones,  some  such  initial 
cause  as  being  blown  up  or  buried  is  ascertainable. 
A  large  proportion  of  these  patients  do  not  recover  in 
a  relatively  short  time,  as  would  be  expected,  were 
this  the  only  cause,  but  on  the  contrary  they  are  often 
difficult  to  treat  and  their  cure  is  notoriously  slow. 
It  is  justifiable  to  assume,  therefore,  that  the  primary 
cause  has  led  to  the  initiation  of  a  cycle  of  processes, 
either  physical  or  psychical,  or  both,  and  that  this 
causes  an  enduring  abnormality  of  functioning.  In 
other  words,  either  an  hysteria,  a  psychasthenia,  or 
a  disturbance  of  physical  harmony  has  resulted. 

In  employing  the  term  "  shell-shock,"  therefore,  we 
shall  confine  its  use  to  those  cases  presenting  definite 
signs  of  cerebral  or  spinal  trauma — the  immediate 
effects  being  unconsciousness,  with  stertorous  breath- 
ing, which  may  or  may  not  lead  to  death.  If  the 
patient  survives,  he  is  left  with  a  variety  of  symptoms 
— some  of  which,  at  any  rate,  are  directly  due  to  a 
*  Hurst,  Brit.  Med.  Journ.,  No.  2961,  p.  413. 


THE  ENDOCEINE  GLANDS  255 

mental  disturbance  supervening  on  the  initial  shock. 
Among  these  are  included  such  various  symptoms  as 
partial  or  complete  amnesia,  persistent  headache,  etc. 
The  "  battle- dreams,"  which  are  so  common  a  feature 
of  these  cases,  point  to  a  definite  mental  mechanism, 
which  is  best  explained  by  the  Freudian  theory  of 
repression.* 

These  cases,  therefore,  by  the  time  they  reach  the 
base  hospitals,  may  be  considered  as  examples  of 
complicated  psycho-physical  disturbance.  Somewhere 
in  the  etiological  chain  is  found  a  disturbed  endocrine 
balance.  It  may  be  that  the  timorous  individual 
has  been  stimulating  his  adrenals  for  a  consider- 
able time  before  he  actually  comes  under  fire,  thus 
paving  the  way  for  an  early  breakdown.  This  would 
account  for  those  patients  who  suffer  from  a  psycho- 
neurosis  after  only  a  few  hours  or  days  in  the  front 
line. 

The  length  of  time  a  soldier  has  served  without  a 
breakdown  is  some  slight  indication  as  to  the  main 
chain  of  cause  in  his  condition.  A  case  which  breaks 
down  at  the  first  test  may  be  assumed  to  be  composed 
primarily  of  psychological  factors,  unless  a  definite 
history  is  obtainable  of  actual  trauma  from  an  ex- 
plosion, fall  of  earth  or  debris,  etc.  In  the  nomen- 
clature here  adopted  this  case  would  fall  into  one  of 

*  All  experiences  painful  to  the  individual  are  repressed  into 
the  unconscious:  they  are  subsequently  prevented  from  re- 
appearing by  the  "censure";  but  this  latter  is  weakened 
during  sleep,  enabling  the  painful  experiences  to  emerge  in 
dreams. 


256   THE  OKGANS  OF  INTERNAL  SECRETION 

the  subdivisions  of  the  psycho-neuroses,  according  to 
the  particular  symptoms  present. 

It  has  been  noticed  and  recorded  by  more  than  one 
observer  that  the  wounded  who  have  been  blown  up, 
buried,  or  otherwise  exposed  to  the  stresses  of  the 
firing-line,  show  a  much  smaller  percentage  of  nervous 
disturbance  than  the  unwounded.  In  other  words,  in 
those  men  suffering  solely  from  "  shell-shock,"  we  are 
justified  in  assuming  some  predisposing  factors.  Some 
of  these  factors  we  shall  outline  in  a  subsequent 
section. 

To  recapitulate  our  nomenclature,  therefore,  we  can 
divide  these  cases  as  follows,  utilizing  a  scheme  of  the 
kind  given  on  p.  257. 

The  term  "  shell-shock  "  will,  in  this  way,  be  con- 
fined to  a  more  or  less  transitory  condition,  and  will 
pass  on  to  one  of  the  following: 

1.  Speedy  recovery. 

2.  Definite  concussion. 

3.  The    appearance    of    symptoms    of    the 

psycho-neuroses. 

In  either  of  the  second  or  third  possibilities  the 
patients  may  develope  symptoms  which  will  be  lengthy 
in  their  duration.  This  may  be  assumed  to  be  the 
most  marked  difference  between  the  first  on  the  one 
hand,  and  the  second  and  third  on  the  other;  and  it 
is  here  submitted  that  one  factor  in  the  determination 
of  such  cases  is  that  the  disturbance  has  been  trans- 
mitted to  the  endocrine  glands.    In  many  instances 


THE  ENDOCEINE  GLANDS 


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258   THE  OEGANS  OF  INTERNAL  SECRETION 

this  is  obviously  so.  but  it  is  here  contended  that  this 
probably  occurs  in  many  more  cases  than  are  recog- 
nized as  possessing  such  a  factor. 

In  making  this  statement,  the  writer  is  far  from 
wishing  to  decry  the  obvious  psychic  element,  or  to 
attribute  the  symptoms  and  their  resistance  to  treat- 
ment solely  to  the  physical.  The  mental  conflict 
which  exists  in  many  of  the  war  neuroses  is  so  marked 
that  any  observant  person  cannot  fail  to  see  that  this 
at  least  is  one  element  (the  same  can  with  equal  truth 
be  said  about  many  civilian  cases).  But  our  object 
is  to  emphasize  the  fact  that  the  case  does  not  begin 
and  end  there.  As  an  electric  current  flows  from  one 
level  to  another,  so  the  disturbance  of  mental  harmony 
flows  to  the  next  level  via  the  sympathetic,  affecting 
the  adrenals,  the  thyroid  and  other  endocrine  glands. 
The  result  is  tins :  that  when  such  a  case  has  persisted 
for  any  length  of  time,  it  is  extremely  unlikely  that 
the  disorder  has  remained  confined  to  the  primary 
centre,  but  has  in  all  probability  succeeded  in  affecting 
other  systems  interdependent  upon  it,  producing  a 
psycho- physical  disturbance. 

This  is  an  important  point,  and  one  which  is  liable 
to  be  overlooked;  the  advocates  of  psychological 
causes  and  treatment  confining  themselves  to  methods 
congenial  to  themselves,  while  the  opposite  school  of 
thought  pins  its  faith  on  the  open-air-free-from-worry- 
tepid-bath  method. 

As  is  often  the  case,  the  middle  course  (if  it  includes 
both)  is  desirable,  for  the  reason  just  given.     In  all 


THE  ENDOCEINE  GLANDS  259 

long-standing  cases,  it  is  a  moral  certainty  that  the 
disturbance  ought  to  be  attacked  from  both  aspects,  as 
by  the  time  it  reaches  this  stage,  it  will  be  a  compound 
of  both  mind  and  body. 

Psychological  Factors. 

In  this  connection,  we  will  confine  our  attention  to 
the  nervous  disorders  arising  in  connection  with  the 
war,  for  the  reason  that  they  are  extraordinarily 
common  at  the  moment  of  writing,  and  much  of  what 
is  here  said  about  such  cases  is  applicable,  with  slight 
adjustments,  to  the  analogous  cases  met  with  in  civil 
life. 

In  attempting  to  understand  the  causation  of  the 
psycho-neuroses,  it  is  of  vast  importance  to  commence 
by  realizing  as  many  of  the  factors  as  possible  which 
exert  their  influence  on  the  psycho-physical  harmony. 
To  do  this  we  must  glance  briefly  at  the  outside 
influences,  and  realize  how  they  react  on  the  individual 
as  a  whole. 

In  his  excellent  work  on  "  Social  Psychology," 
Professor  McDougall  deals  very  fully  with  the  instincts. 
He  describes  the  primary  instincts,  with  their  attached 
emotions;  the  secondary  instincts,  and  the  "pseudo- 
instincts."*  He  points  out,  for  instance,  that  the 
instinct  of  flight  leads  to  the  emotion  of  fear;  that 
the  instinct  of  pugnacity  is  related  to  the  emotion  of 
anger;  and  that  of  repulsion  to  the  emotion  of  disgust. 

*  "  Social  Psychology,"  by  W.  McDougall,  F.R.S.    (Methuen.) 


260   THE  OEGANS  OF  INTEENAL  SECEETION 

In  the  turmoil  of  modern  warfare,  the  soldier  ex- 
periences psychical  stimuli  which  he  rarely  encounters 
in  civil  life.  He  is  constantly  facing  danger,  and  is 
frequently  "  up  against  "  countless  threats  to  his  self- 
preservation;  in  other  words,  his  instinct  of  flight  is 
constantly  aroused.  But,  with  the  tradition  of  his 
land,  the  self-respect  he  possesses,  and  the  help  afforded 
by  that  deep-rooted  force  which  Mr.  Trotter  has 
named  the  herd  instinct,*  the  corresponding  emotion 
of  fear  is  kept  in  check. f  But  the  stimulation  is 
transmitted  to  the  physical  system.  Fear  has  been 
shown  to  produce  an  increase  in  the  quantity  of 
adrenalin  secreted.  The  physiological  object  sub- 
served is  to  afford  the  organism  greater  muscular 
energy,  which  can  be  expended  in  satisfying  the 
demands  of  the  instinct  under  stimulation — in  other 
words,  it  enables  the  individual  to  take  refuge  in 
flight. 

*  "  The  Herd  Instinct  in  Peace  and  War,"  by  W.  Trotter. 
(Fisher  Unwin,  London.) 

f  This  is  not  the  place  to  discuss  the  fascinating  theory  of 
"conflict,"  which  attempts  to  explain  the  physical  symptoms 
of  nervous  disorders  as  resultants  of  mental  conflict  between 
two  instincts.  In  war  cases,  the  instincts  most  frequently 
concerned  are  those  of  self-preservation  and  self-respect.  We 
may  draw  attention  in  passing  to  one  fact  pertinent  to  our 
present  inquiry — namely,  that  the  individual  who  is  constantly 
receiving  stimuli  to  a  deeply-rooted  instinctive  disposition, 
such  as  that  of  self-preservation  (the  results  of  such  stimulation 
being  guided  from  their  normal  psychological  course  by  con- 
scious control),  will,  in  turn,  pass  on  such  stimulation  to  physio- 
logical mechanisms,  with  the  results  we  are  now  studying. 


THE  ENDOCEINE  GLANDS  261 

The  Psycho-Physiological  Mechanism. 

Fear,  then,  may  be  regarded  as  leading  to  definite 
sequelae.  In  like  manner,  other  instinctive  processes 
produce  similar  bodily  manifestations,  as  reactions  of 
mind  on  body.  Such  reactions  are  biologically  useful, 
and  definitely  subserve  useful  purposes — e.g.,  the 
preservation  of  the  individual. 

We  have  already  seen  the  close  morphological  and 
physiological  relations  existing  between  the  adrenals 
and  the  sympathetic  nervous  system.*  Now,  the 
sympathetic  is  stimulated  by  emotion.  This  stimula- 
tion is  shared  by  the  adrenals,  through  their  sympa- 
thetic supply;  and  this  in  turn  leads  to  a  flow  of 
adrenalin.  This  flow  is  additional  to  the  steady 
secretion,  which  has  been  shown  to  take  place  and 
to  exert  a  continuous  tonic  influence  on  the  sym- 
pathetic. 

The  additional  supply  of  adrenalin,  in  company  with 
the  sympathetic  activity  distributed  to  all  the  un- 
striped  musculature,  enables  the  organism  to  put 
forth  an  increased  amount  of  energy.  This  should 
normally  be  used  in  satisfying  the  instinct  under 
stimulation  at  the  time:  in  the  present  instance  the 
fear  should  be  satisfied  by  flight. 

But,  to  revert  for  a  moment  to  the  case  of  the 
soldier,  with  the  resulting  emotion  held  firmly  in 
check  by  conscious  control,  some  alternative  scheme 
must  be  utilized,  when  the  normal  sequence  is,  as  in 

*  Chapter  XL,  p.  232. 


262  THE  ORGANS  OF  INTERNAL  SECRETION 

the  present  instance,  unavailable.  The  energy  thus 
created  is  not  utilized;  and  there  then  exists  a  mass 
of  available  energy  which,  if  not  expended  in  some 
other  channel,  must  be  dammed  up.  This  is  what 
appears  to  happen  in  many  cases  of  war-shock.  The 
patient  is  restless,  on  the  qui  vive  at  every  sound, 
flushes  easily,  has  tachycardia  at  the  slightest  exertion — 
in  fact,  resembles  strikingly  the  description  given  in 
Chapter  III.  of  the  patient  suffering  from  Graves' 
disease.*  In  other  words,  his  psycho-physical  ap- 
paratus has  been  attuned  for  the  biological  purpose 
of  sudden  action,  but  this  action  has  not  come  to 
pass. 

The  physiological  mechanism  which  produces  this 
energy  is  now  well  understood.  The  activity  of  the 
suprarenal  glands,  in  company  with  the  sympathetic 
stimulation,  enables  the  individual  to  perform  feats 
of  unusual  strength  (more  particularly  under  sudden 
stress)  in  response  to  the  emotions  engendered,  as  we 
have  already  seen,  by  instinctive  reactions.  Again, 
the  stimulation  of  the  sympathetic  produces  splanchnic 
vaso-constriction,  with  an  increased  systemic  blood- 
pressure;  there  is  increased  rapidity  in  the  heart-beat; 
and  an  increased  quantity  of  sugar  becomes  converted 
from  the  hepatic  glycogen  by  means  of  the  hyper- 
adrenia,  and  available  for  muscular  energy. 

Sweating,  which  takes  place  on  exertion,  keeps  the 
temperature  normal. 

At  this  stage,  then,  the  individual  is  prepared  to 

*  P.  55  et  seq. 


THE  ENDOCRINE  GLANDS  263 

react  to  his  environment.  In  the  war  cases,  we  repeat, 
the  normal  reaction  would  be  one  of  two  courses. 
Either  the  soldier  would  react  by  evincing  anger  and 
thus  temporarily  increase  his  military  efficiency,  or 
he  would  utilize  his  additional  energy  in  night.  In 
the  former  case,  he  is  enabled  to  meet  adequately  the 
enormous  demands  made  upon  his  endurance;  in  the 
latter  (where  flight  is  resisted),  the  baulked  emotion 
produces  a  condition  which  the  psychologists  regard 
as  a  mental  conflict,  and  the  physiologists  as  an 
auto-intoxication  from  perverted  hormones. 

The  plain  fact  appears  to  be,  however,  that  the 
mental  conflict  is  the  primary  and  more  fundamental 
origin  in  these  war  cases,  leading  by  a  natural  reaction 
to  bodily  changes,  which,  if  denied  an  outlet,  recoil 
on  the  psyche  and  produce  a  condition  which  is  thus 
seen  to  be  made  up  of  mental  and  physical  elements. 

The  emotions  thus  aroused  lead  to  continued  over- 
activity of  the  thyroid  and  suprarenal  glands,  and 
the  glandular  system  so  stimulated  is  like  a  lake  over- 
full which  is  ever  threatening  to  overflow  and  work 
destruction  for  the  want  of  a  normal  outlet.  Hence 
we  see  in  many  cases  of  nervous  disorders  produced 
by  the  war,  such  symptoms  as  sudden  "  starts," 
myoclonic  spasms,  tremors  of  all  kinds,  and  restless 
movements.  Again,  the  mental  elements  concerned  are 
active  in  sleep,  producing  startling  panoramas,  which 
again  lead  to  further  thyroid  and  adrenal  secretion.* 

*  This  was  well  shown  in  a  soldier  under  my  care  in  France. 
This  patient  had  been  rendered  unconscious  by  the  explosion 


264  THE  ORGANS  OF  INTERNAL  SECRETION 

Thus,  to  a  certain  extent,  the  mental  and  bodily 
conditions  react  upon  each  other,  producing  a  vicious 
circle  of  auto-stimulation. 

Hyperthyroidism  and  the  Neuroses. 

It  has  already  been  said  that  many  patients  suffering 
from  war  neurosis  evidence  the  signs  and  symptoms  of 
Graves'  disease.  We  have  already  described  these  in 
some  detail;*  and  we  will  here  content  ourselves  by 
emphasizing  some  important  points  arising  in  this 
connection. 

From  the  earliest  recorded  accounts  of  this  disease, 
it  is  quite  clear  that  the  symptoms  referable  to  the 
nervous  system  were  always  prominent.  From  the 
description  in  Chapter  III.  the  reader  will  see  that 
stress  was  there  laid  upon  this  group  of  symptoms. 
The  difficulty  which  faces  the  student  of  this  disease 
is  one  which  is  encountered  in  almost  every  sphere  of 
medicine — namely,  the  question  of  the  origin  of  the 
disorder.  Is  it  primarily  psychogenic,  or  are  the 
symptoms  secondaiy  to  disordered  physical  functions  ? 

of  a  shell  and  had  been  left  with  a  retrograde  local  amnesia. 
He  had  an  "  electric-like  "  twitching  of  the  muscles  of  the  right 
side  of  the  neck  and  right  shoulder,  which  only  disappeared 
when  the  blank  in  his  memory  was  filled  in.  The}^  recurred, 
however,  after  a  disturbing  dream,  but  again  vanished  after 
treatment  directed  to  the  mental  content.  After  each  such 
dream  the  patient  showed  evident  signs  of  an  increased  adrenal 
secretion,  but  was  finally  cured  by  psycho-therapy,  with  the 
abolition  of  all  his  symptoms. 
*  Chapter  III.,  p.  55  et  seq. 


THE  ENDOCRINE  GLANDS  265 

In  speaking  of   the  difficulty  of   deciding  this  point, 
the  writer  of  a  recent  article  says : 

11  This  (the  work  of  Cannon)  demonstrates  how 
complete  is  the  cycle,  and  how  difficult  it  is  in  a  given 
case  to  ascertain  whether  the  original  cause  was 
psychical  or  material.  In  no  disease  is  this  more 
evident  than  in  Graves'  disease.  Here  a  succession  of 
nervous  shocks  may  excite  the  adrenals  until  the 
thyroid  is  put  into  action,  and  the  threshold  of  its 
action  permanently  lowered — with  the  attendant 
phenomena  of  hyperthyroidism.  But  again  the  stimu- 
lation of  the  vagus  may  come  from  so  material  a  source 
as  a  uterine  myoma,  or  other  pelvic  irritation — as 
Hertzler  pointed  out.  But  the  outcome  is  the  same; 
the  thyroid  becomes  stimulated  until  its  threshold  is 
permanently  lowered."* 

We  have  already  pointed  out  that  the  reasons  for 
regarding  many  of  the  war  cases  as  primarily  psycho- 
genic are  ample:  the  same  would  apply  to  those  cases 
of  Graves'  disease  among  soldiers.  It  is  a  well-known 
fact  that  the  syndrome  which  we  have  hitherto  called 
"  hyperthyroidism "  is  frequently  met  with  among 
the  cases  of  functional  neuroses  which  arrive  at  the 
base  hospitals;  and  the  present  writer  has  no  hesita- 
tion in  saying  that  if  these  cases  are  carefully  examined 
a  certain  proportion  will  show  a  clinical  picture  not 
differing  in  any  marked  manner  from  the  pre-war 
Graves'  disease.  The  exophthalmos  is  not  often 
marked,  but  the  fine  tremor,  moist  skin,  tachycardia, 

*  Editorial,  Endocrinology,  October-December,  1917,  p.  402. 


266    THE  OEGANS  OF  INTERNAL  SECRETION 

prominent  thyroid,  and  mental  irritability  are  all 
present.  The  brisk  reaction  to  any  emotional  excite- 
ment, with  exaggeration  of  those  features,  shows  that 
the  mental  element  is  not  negligible.  Furthermore, 
anyone  who  has  had  any  lengthy  experience  of  this 
class  of  soldier-patient  will  agree  that  his  mental 
outlook  is  markedly  similar  to  that  of  the  civilian 
patient  with  exophthalmic  goitre. 

It  is  difficult  to  say  which  symptoms  owe  their 
origin  to  the  hyperadrenalism  and  which  to  the  hyper- 
thyroidism; but  the  blood-pressure  of  these  patients 
is  nearly  always  above  normal.  Among  these  patients, 
moreover,  many  will  complain  mainly  of  the  cardiac 
discomfort,  with  the  result  that  not  a  few  reach 
the  hospitals  labelled  "  disordered  action  of  the 
heart," 

Whatever  part  in  the  circle  these  two  glands  play, 
their  role  is  obviously  an  important  one,  and  due 
consideration  is  necessary  in  deciding  upon  the  line 
of  treatment  to  be  adopted  in  such  a  case.  Rest 
would  appear  to  be  essential  in  the  early  cases;  and 
Black  records  the  case  of  a  goitre  which  disappeared 
entirely  when  adrenalin  chloride  solution  was  given.* 
Such  treatment,  however,  should  be,  in  the  present 
writer's  opinion,  entirely  secondary  to  treatment 
directed  to  the  mental  factors,  and  the  rapid  improve- 
ment in  physical  symptoms  (i.e.,  tachycardia,  sympa- 
thetic irritability,  etc.)  which  has  followed  judicious 
treatment   directed  to  the  mental  state  in  the  war 

*  New  York  State  Journal  of  Medicine,  1917.  xvii.  125. 


THE  ENDOCEINB  GLANDS  267 

cases,  leads  him  to  believe  that,  in  a  certain  proportion 
of  these  cases  at  any  rate,  the  mental  turmoil  is  the 
primary  factor. 

Dementia  Prsecox. 

Any  account  of  the  relation  between  the  ductless 
glands  and  the  neuroses  which  omitted  some  mention 
of  this  disorder  would  be  incomplete.  For  the  evidence 
that  the  endocrine  glands  fit  in  somewhere  in  the 
chain  of  cause  and  effect  is  very  striking. 

In  order  to  avoid  a  lengthy  discussion,  we  will 
confine  ourselves  to  an  attempt  to  draw  the  reader's 
attention  to  some  salient  features  of  this  disease  which 
appear  to  be  directly  traceable  to  an  upset  endocrine 
balance. 

1.  The  disease  is  essentially  a  disease  commencing 
in  adolescence;  in  other  words,  when  the  fresh  internal 
secretions  make  their  appearance,  and  when  they  are 
not  "  assimilated  "  to  the  existing  system,  they  are 
capable  of  disturbing  the  normal  balance.* 

2.  The  internal  secretion  of  the  sex  glands  introduces 
at  puberty  fresh  elements  into  the  hormonic  system. 

3.  This  additional  and  vigorous  appeal  is  such 
that  the  cerebral  neuronic  representatives  must  suffer 
strains  in  their  endeavour  to  meet  this  call  with  a 
corresponding  vigour  of  inhibition. 

4.  An  accumulation  of  affective  tension  or  sub- 
conscious emotion,  is  brought  about. 

*  Many  of  the  following  points  are  quoted  from  an  interesting 
paper  by  Dunlop  Robertson  in  the  Journal  of  Mental  Science 
for  July,  1915,  pp.  392  et  seq. 


268   THE  OEGANS  OF  INTERNAL  SECRETION 

5.  The  physiological  channel  of  outlet  for  sub- 
conscious emotion  is  the  sympathetic  nervous  system. 

6.  The  chromaffin  cells,  being  developmentally 
closely  associated  with  the  sympathetic  nerve-cells, 
will  feel  the  hereditary  biological  handicap  almost,  if 
not  quite,  as  severely  as  the  neuronic. 

7.  There  will  therefore  be  a  hypersecretion  of  adrenalin, 
which,  in  excess  of  the  bodily  requirements,  is  a  toxin. 

In  criticizing  the  above  views,  it  is  necessary  to 
remember — 

(a)  That  adrenalin  acts  quickly  and  for  a  short 
period  only. 

(b)  That  it  is  quickly  oxidized. 

Unless  the  "  hereditarily  transmitted  defective 
biochemism  "*  alters  this  property  of  adrenalin,  it  is 
a  little  difficult  to  understand  why  it  produces  the 
features  of  dementia  prsecox,  which  this  writer  attri- 
butes to  it,  and  why  it  does  not  produce  the  thyroid 
reaction  which  it  does,  in,  e.g.,  the  war  neuroses. 

Again,  this  author  believes  that  the  hypersecretion 
of  adrenalin  leads  to  a  cerebral  anaemia,  and  there  is 
a  good  deal  of  recent  evidence  to  support  the  view 
that  there  are  vaso-motor  fibres  in  the  brain,  f  If  this 
is  so,  there  is  some  reason  to  believe  that  a  condition 
of  cerebral  anaemia  might  follow  the  hypersecretion 
of  adrenalin. 

In  speaking  of  the  emotional  symptoms  of  dementia 

*  To  which  Dunlop  Robertson  refers. 

t  See  an  interesting  article  by  Orr  and  Rows  in  Brain,  vol.  xli., 
part  i.,  1918,  entitled  "  The  Interdependence  of  the  Sympathetic 
and  Central  Nervous  Systems." 


THE  ENDOCEINE  GLANDS  269 

praecox  Kobertson  says:  "  The  subterranean  lake,  then 
of  vagrant  and  vibrant  emotion,  gets  vent  for  its 
excess  by  welling  up  on  to  the  physical  surface,  through 
the  physiological  channel  of  the  sympathetic.  The 
stimulant  sympathetic  finds  expression  through  the 
functioning  of  its  peripheral  end-organs,  and  of  these 
the  chromaffin  cells  (which  accompany  the  ramifica- 
tions of  the  sympathetic,  which  are  so  strongly  repre- 
sented in  the  medulla  of  the  suprarenal  capsules,  and 
which  are  developmentally  so  closely  associated  in 
origin  with  the  sympathetic  nerve- cells  themselves) 
are  notable  and  important  members.  (We  believe 
these  chromaffin  cells  are  first  recorded  as  low  down 
in  the  zoological  scale  as  the  amphibia.)  One  of  their 
specific  functions  is  to  secrete  adrenalin,  which  by  the 
suprarenal  vein  gains  the  inferior  vena  cava,  and 
thence,  the  general  blood-stream.  .  .  . 

"  The  access  of  an  additional  and  continuous  psychic 
stream  of  stimulation  through  the  sympathetic  to  its 
end-organs  will  upset  the  cyclic  balance,  and  cause 
excessive  elaboration  and  secretion  of  adrenalin  as  a 
functional  response.  The  affinitive  derivation  of  these 
cells  to  the  neuronic  will  certainly  imply  their  almost 
as  easy  susceptibility  to  the  biological  handicap  as  the 
neuronic  cells  themselves.  .  .  .  Their  '  irritability 
of  weakness  '  being  seen  in  hypers ensitiveness  to 
stimulus,  as  hypersecretion  at  first,  perhaps  later  on 
as  hypos ecretion."* 

Swale   Vincent,|   in   discussing   an   experiment    by 

*  Robertson,  ibid.,  p.  399.  f  Ibid. 


270   THE  OEGANS  OF  INTERNAL  SECRETION 

Dreyer,  Asher,  and  Tschehoksaroff,  says:  "  The  adrenal 
secretion  is  under  the  control  of  the  thoracico-lumbar 
sympathetic  system.  They  further  call  attention  to 
the  fact  that  the  phenomena  of  a  major  emotional 
condition,  in  an  animal,  indicate  the  dominance  of 
sympathetic  impulses.  When,  for  example,  a  cat 
becomes  frightened,  the  pupils  dilate,  the  stomach  and 
intestines  are  inhibited,  the  heart  beats  rapidly,  the 
hair  of  the  back  and  tail  stands  erect — all  signs  of 
nervous  discharge  along  sympathetic  paths." 

I  have  quoted  at  some  length  from  this  article 
because  I  desired  to  emphasize  the  theoretical  relation 
of  the  internal  secretions  to  a  psychosis.  Dementia 
praecox  is  the  most  suitable  mental  disorder  to 
discuss  in  this  relation,  as  its  origin  is  still  in  dis- 
pute. The  theories  of  its  genesis  are,  broadly, 
three  :* 

1.  The  toxin  theory,  which  maintains  that  the 
disease  is  due  to  toxins  acting  on  the  nervous  mechan- 
ism, either  through  the  nutrient  fluid  or  through  the 
organs  of  internal  secretion. 

2.  The  "  inherently-  defective  "  theory. 

3.  The  psychogenic  theory. 

Abderhalden  believes  that  this  disease  owes  its 
origin  to  a  "  dysfunction  of  the  sex  glands,"  and  the 
tests  carried  out  by  H.  Cotton,  Corson  White,  and 
W.  W.  Stevenson  appear  to  bear  this  out.  The  results 
of  the  Abderhalden  tests  showed — 

1.  That  this  test  gives  certain  definite  results. 
*  Langdon,  Amer.  Jour,  of  Insan.,  1917,  April. 


THE  ENDOCBINE  GLANDS  271 

2.  That  these  results  were  practically  negative 
except  in  dementia  prsecox  and  epilepsy. 

3.  That  in  the  former  condition  81  per  cent,  showed 
abortive  reaction  to  sex  glands,  and  3  out  of  55  gave 
abortive  reaction  to  both  thyroid  and  sex  glands.* 

These  experiments  certainly  support  the  view  that 
the  ductless  glands  are  vitally  concerned  in  the  etiology 
of  dementia  prsecox,  and  for  this  reason  we  have  here 
quoted  them. 

It  is  obvious,  therefore,  that  its  relation  to  the 
neuroses  we  have  been  considering  is  fairly  close,  in 
so  far  as  the  internal  secretions  are  concerned — that 
is  to  say,  that  some  authors — e.g.,  Dunlop  Robertson — 
lay  stress  "upon  the  predominant  part  played  by  the 
adrenal  secretions;  while  others  emphasize  the  part 
played  by  sex  organs.  For  this  reason,  and  to  make 
our  general  survey  in  this  chapter  more  complete,  a 
brief  discussion  of  this  disorder  was  deemed  advisable. 

Summary. 

We  will  now  recapitulate  the  main  points  dealt 
with  in  this  chapter,  and  briefly  suggest  some  possible 
lines  of  treatment. 

In  any  case  of  functional  neurosis,  whether  it  be 
hysteria,  psychasthenia,  neurasthenia,  or  (in  soldiers) 
the  sequelae  of  "  shell-shock,"  or,  again,  those  border- 
line cases  which  may  be  regarded  as  dementia  prsecox, 
it  is  important  to  remember  that  we  have  no  right 

*  Amer.  Jour,  of  Insan.,  January,  1917,  p.  472. 


272   THE  OEGANS  OF  INTBENAL  SECEETION 

to  state  dogmatically  that  the  disease  is  solely  psycho- 
genic or  solely  physicogenic.  Our  knowledge  of  these 
disorders  is  increasing  daily,  but  even  now  we  have 
insufficient  information  to  warrant  us  in  stating 
arbitrarily  that  either  origin  is  the  only  and  exclusive 
one  in  a  given  case. 

This  being  true  for  the  majority  of  such  cases,  it 
is  a  good  working  rule  to  keep  in  mind  that  whereas 
treatment  from  both  view-points  can  do  no  harm  if 
kept  under  careful  observation,  treatment  from  one 
only  may  very  well  prove  inefficacious.  To  illustrate 
tins  point,  I  may  perhaps  quote  a  case  which  I  have 
recently  been  asked  to  see.  The  patient  was  a  young 
soldier,  who  had  returned  from  France  with  "  shell- 
shock  "  some  few  weeks  ago.  He  informed  me  that 
he  had  always  been  "  rather  nervous,"  but  had  enjoyed 
good  health  previous  to  joining  the  Army.  He  had 
been  in  France  about  five  months,  the  first  four  of 
which  he  had  spent  behind  the  line.  He  had  only 
been  in  the  firing-line  a  few  days  when  three  shells 
burst  near  him,  and  he  lost  consciousness.  From  a 
close  inquiry,  it  appeared  that  the  shells  did  not 
explode  particularly  near  him,  and  certainly  he 
suffered  from  no  actual  trauma  or  gas  poisoning.  He 
regained  consciousness  on  reaching  the  hospital,  and 
from  there  was  eventually  invalided  home. 

When  I  saw  him  his  condition  had  lasted  nearly 
two  months,  and  as  he  well  illustrates  the  combination 
of  psycho-physical  elements,  I  will  briefly  describe 
his   symptoms.     He   was    twenty- two    years   of   age, 


THE  ENDOCEINE  GLANDS  273 

rather  poorly-nourished,  with  a  high  colour  and  a 
good  head  of  hair.  The  pulse  was  full  and  rapid 
(110  per  minute),  and  he  complained  of  palpitation. 
The  skin  was  soft  and  moist,  and  he  suffered  from 
undue  sweating  on  any  exertion.  There  was  polyuria 
and  frequency  of  micturition.  The  thyroid  gland  was 
obviously  enlarged :  and  there  was  a  fine  tremor  of  the 
hands. 

In  addition  to  these  symptoms  this  patient  suffered 
from  periodic  "  attacks,"  which,  from  the  description 
of  his  medical  officer,  were  undoubtedly  hysterical  in 
character.  I  did  not  witness  any  of  these  attacks 
myself. 

The  clinical  picture  was  interesting  and  exemplifies 
well  the  combination  already  referred  to.  This  patient 
"  broke  down  "  at  practically  the  first  shelling  to 
which  he  was  exposed;  and  I  have  little  doubt  that 
his  timorous  soul  had  been  flogging  his  adrenals  for 
some  weeks  before  he  was  actually  under  fire.  The 
experiences  he  underwent  were  probably  stored  and 
revived  in  the  hysterical  "  attacks."  But  the  physical 
signs  were  strongly  suggestive  of  adrenal  and  thyroid 
excess.  The  combination  of  mental  and  physical 
signs  pointed,  in  my  opinion,  to  the  conclusion  that 
the  initial  step  in  the  development  of  this  neurosis 
had  been  mental;  the  continual  fear  had  led  to 
hyperadrenalism,  and  when  I  saw  this  patient  both 
psychical  and  physical  elements  were  in  full  swing. 

I   refer  to  the   case   as   typical  of  numerous   war 
neuroses,  and  because  it  is  an  instance  of  a  disorder 

18 


274  THE  ORGANS  OF  INTERNAL  SECRETION 

showing  the  combined  symptoms.  It  will  be  noted 
that  the  condition  had  been  in  existence  for  nearly 
two  months  when  I  saw  the  patient,  and  consequently 
the  hyperadrenalism  had  had  time  to  "  whip  up  "  the 
thyroid,  with  resulting  enlargement  of  the  latter. 

There  is  a  good  deal  of  divergence  of  opinion  with 
regard  to  the  treatment  of  such  cases.  The  broad 
lines  only  can  be  laid  down  here,  and  in  Chapters  XIII. 
and  XIV.  will  be  found  a  summary  of  organo-therapy. 
A  few  additional  remarks  may  be  helpful. 

So  far  as  general  treatment  is  concerned,  it  is  a  good 
rule  that  such  patients  must  on  no  account  be  allowed 
to  exert  themselves  beyond  a  safe  margin,  so  long  as 
there  are  any  signs  of  tachycardia,  undue  sweating, 
or  restlessness.  Those  cases  showing  none  of  these 
signs,  and  especially  cases  of  more  or  less  pure  hysteria, 
must  on  no  account  be  allowed  to  remain  in  bed  or 
in  any  other  avoidable  way  to  depart  from  the  routine 
of  everyday  life. 

We  can  perhaps  best  summarize  the  treatment  as 
follows,  but  it  must  be  understood  that  no  attempt 
is  here  being  made  to  indicate  in  what  cases  any 
particular  treatment  is  indicated. 

I. — General  Methods. 

These  include  such  simple  but  nevertheless  im- 
portant questions  as  Rest  or  Exercise,  methods  of 
handling  the  patient,  and  the  general  basis  on  which 


THE  ENDOCRINE  GLANDS  275 

subsequent  treatment  can  be  built.  Isolation  can  be 
used  in  suitable  cases,  and  combined  with  "  sugges- 
tion "  (see  next  section)  is  of  great  help  in  hysteria. 
For  cases  of  hyperadrenalism,  rest  in  the  early  stages 
is  essential,  and  in  all  cases  associated  with  rapidity 
of  the  heart's  action,  the  return  to  a  normal  life  of 
exertion  must  be  graduated. 

The  neurasthenic,  especially  the  hypochondriacal 
type,  must  never  be  isolated,  but  must  be  firmly 
treated  by  a  due  (not  exaggerated)  attention  to  the 
excretory  organs,  with,  so  far  as  it  is  possible,  every 
encouragement  to  turn  his  attention  to  his  environ- 
ment, which  should  therefore  be  made  more  attractive 
than  his  viscera. 

II. — Psycho-  Therapy. 

This  type  of  treatment  may  be  divided  into  three: 
Suggestion,  Persuasion,  and  Analysis.  For  the  hysteri- 
cal and  psychasthenic  patient  one  or  other  of  these 
methods  holds  out  the  best  hope.  Such  patients 
invariably  benefit  from  these  forms  of  treatment;  and 
usually  if  the  mental  treatment  deals  with  the  primarj^ 
causation,  the  secondary  results  will  require  further 
treatment. 

For  such  patients  most  physical  treatments  should 
be  accompanied  by  a  large  dose  of  suggestion.  Elec- 
tricity, drugs,  and  diet  should  all  be  utilized  so  as  to 
convey  helpful  suggestion. 

In  a  condition  of  obvious  psychogenic  origin, 
probably   some   superficial    psycho-analysis    may    be 


276   THE  ORGANS  OF  INTERNAL  SECRETION 

very  helpful  at  the  start.  It  is,  in  the  writer's  opinion 
and  experience,  not  contra-indicated  in  war  cases  of 
this  nature,  and  the  patient  is  far  more  likely  to  reach 
a  higher  mental  level,  when  the  causative  mental 
factors  have  been  dealt  with,  than  he  is  if  treated 
solely  by  some  indirect  method  such  as  rest  and  fresh 
air.  It  must  be  borne  in  mind  that  these  patients 
have  had  to  undergo,  certainly  in  many  instances,  a 
mental  and  physical  strain  such  as  human  beings  have 
seldom  previously  been  subjected  to.  Confessions  of 
their  troubles  is  a  source  of  great  help  to  them,  and 
the  sympathetic  and  intelligent  explanation  of  these 
troubles  does  more  to  assist  the  beginnings  of  treat- 
ment than  any  tiling  else. 

Persuasion  may  be  regarded  as  the  intelligent 
balancing  of  one  set  of  ideas  by  another — e.g.,  the 
convincing  of  a  hysterical  paraplegic  that  his  muscles 
are  not  paralyzed,  but  only  appear  so  to  him. 

Suggestion — waldng  and  hypnotic — are  both  useful 
in  selected  cases,  and  have  their  field  of  usefulness  in 
almost  every  variation  of  these  disorders. 

Ill Physical  Therapy. 

Drugs. — The  present  writer's  experience  of  the 
psycho-neuroses,  both  in  civil  life  and  among  war 
cases,  has  led  him  to  the  opinion  that  this  branch  of 
therapeutics  plays  but  a  subservient  part  in  these 
cases. 

Sedatives  and  tonics  are,  of  course,  indicated  in 
certain  conditions.     But  the  routine  administration  of 


THE  ENDOCBINE  GLANDS  277 

large  doses  of  bromides,  of  valerian,  or  of  strychnine 
and  its  compounds,  has  little  to  recommend  it. 

Were  the  trouble  a  simple  one,  or  one  which  requires 
only  a  little  help  in  the  sedative  or  stimulant  line, 
their  use  would  be  justifiable.  But  this  is  rarely  the 
case  in  such  disorders  as  we  are  discussing;  and  some- 
thing more  than  the  empirical  use  of  drugs  is  indicated. 

Electricity,  Massage,  Physico- therapy . — Such  methods 
as  these  are  of  real  help  in  neurasthenia:  but  should 
not  be  ordered  where  the  symptoms  are  believed  to  be 
mainly  psychogenic,  because  they  tend  to  encourage 
the  belief  that  the  condition  is  organic  and  therefore 
(to  the  patient's  mind)  serious.  Hysteria  and  psych- 
asthenia,  therefore,  are  not  suitable  objects  for  these 
forms  of  treatment,  or  only  so  when  the  early  stages 
of  treatment  by  the  methods  advocated  in  Class  II. 
have  been  initiated. 

Physico-therapy  is  of  great  value  in  the  later  stages 
of  treatment  in  nearly  all  these  cases.  Physical  re- 
education, exercises  and  graduated  drill  fulfil  a  most 
useful  purpose  in  the  restoring  of  tone  to  the  muscular 
and  vascular  systems,  and  indirectly  to  the  jaded 
nervous  system. 

In  this  class  of  treatment,  moreover,  we  might 
emphasize  the  importance  of  remedying  intestinal 
stasis,  with  its  accompanying  toxaemia,  if  there  is 
any  suspicion  of  its  presence.  Many  of  the  patients 
in  these  groups  of  disorders  show  sign  of  intestinal 
stasis  (constipation,  meteorism,  etc.),  and  it  is  of 
importance  that  this  should  be  remedied  at  the  earliest 
possible  moment. 


278   THE  ORGANS  OF  INTERNAL  SECRETION 


IV Orgayio-  Therapy. 

Although  the  various  internal  secretions  play  an 
important  part  in  the  genesis  of  these  disorders,  they 
have  been  left  to  the  last  in  this  summary,  for  their 
administration  has  been  fully  dealt  with  in  the  subse- 
quent chapters,  and  there  are  only  a  few  points  left 
to  be  discussed. 

On  p.  187  we  refer  to  the  use  of  pancreatic  extract 
in  counteracting  hyperadrenalism.  Unfortunately  the 
author  has,  at  present,  had  insufficient  experience  of 
this  mode  of  treatment  to  speak  decidedly  of  its 
effects:  but,  bearing  in  mind  the  large  number  of 
patients  who  exhibit  signs  of  this  condition,  its  ex- 
tended use  might  be  given  a  trial. 

Thyroid- therapy  requires  no  further  mention  here, 
as  there  is  nothing  to  add  to  what  is  contained  in 
Chapters  V.  and  XIII. 

Pituitary  extract  has  a  limited  use.  For  cases  in 
which  this  extract  would  be  suitable,  the  reader  is 
referred  to  Chapter  V. 

The  internal  secretions  of  digestion  are  of  use  in 
these  patients  mainly  where  some  concurrent  dis- 
turbance of  the  functions  of  digestion  are  prominent. 
Their  exhibition  is  as  indicated  in  Chapter  X. 

For  the  neurasthenic  patient,  the  extracts  of  the 
gonads,  either  alone  or  combined  with  extracts  of 
nervous  tissue,  are  frequently  of  the  greatest  help. 
Many  of  the  preparations  referred  to  in  earlier  parts 


THE  ENDOCBINE  GLANDS  279 

of  the  book  will  be  found  to  assist  the  recovery  of 
the  debilitated  patient,  and  so  quicken  the  return  of 
strength  to  the  convalescent  from  a  psycho-neurosis. 

If  the  treatment  of  these  cases  is  roughly  divided 
into  three  stages — viz.,  initial,  mediate,  and  con- 
valescent— we  can  supply  and  helpfully  prescribe  such 
preparations  in  the  third  stage,  and  be  fairly  confident 
that  they  will  assist  in  restoring  the  strength  of  the 
patient. 


CHAPTER  XIII 

THE  THERAPEUTIC  APPLICATION  OF 
HORMONES 

So  far  we  have  dealt  more  with  the  physiological  and 
pathological  aspects  of  the  ductless  glands  and  their 
secretions  than  we  have  with  the  therapeutic  appli- 
cation, while  some  of  the  chapters  have  concerned 
themselves  exclusively  with  diseases  associated  with 
one  or  other  of  the  ductless  glands.  In  this  chapter 
we  propose  to  summarize  the  uses  to  which  prepara- 
tions of  these  glands  can  be  put  in  practice;  and  we 
shall  hope  to  outline  the  more  commonly  used  extracts 
and  to  give  some  indications  of  their  utility. 

From  this  latter  standpoint,  there  can  be  little  doubt 
that  the  thyroid  must  first  claim  our  attention;  for 
this,  of  all  the  endocrine  glands,  gives  the  best  results 
to  administration  of  its  extracts — that  is  to  say, 
administration  over  a  duration  of  time.  In  the 
following  chapter  some  points  in  the  administration 
of  organic  products  are  discussed. 

Now,  what  is  the  rationale  of  hormone-therapy, 
and  with  what  object  do  we  administer  these  extracts  ? 
Harrower  epitomizes  these  questions  in  his  book,  and 
he  divides  "  the  availability  of  hormone  action  "  into 

280 


APPLICATION  OF  HORMONES  281 

four  groups.  The  first  is  "  substitution  therapy  " — 
the  supplying  of  a  missing  hormone  whose  loss  is  due 
to  destructive  lesions  or  other  cause  of  absence  of 
the  organ;  the  second  is  "supplementary  therapy" 
— "  the  augmentation,  directly  or  reflexly,  of  a  pre- 
sumed deficiency  ";  the  third  is  "  specific  physiological 
therapy  " — the  production  of  a  definite  physiological 
influence  which  is  indicated,  but  which  is  not  due  to 
any  change  in  the  normal  hormone  production;  and 
the  fourth  is  "  empirical  therapy."1 

Now,  with  this  distinction  emphasized  we  can  com- 
mence to  study  the  facts  which  have  to  be  considered 
when  we  propose  to  administer  extracts  of  the  ductless 
glands. 

First  of  all,  we  know  that,  with  certain  exceptions, 
these  extracts  are  not  toxic,  although  some  of  them 
have  to  be  given  in  small  doses  and  with  great  care. 
Thus,  thyroid  extract  (as  we  have  frequently  pointed 
out)  must  on  no  account  be  given  in  the  doses  which 
are  still  found  in  books — that  is  to  say,  from  3  to  10 
grains  as  one  dose.  Its  administration  should  take 
the  form  of  fractions  of  a  grain,  certainly  to  commence 
with.  We  shall  go  into  the  details  of  thyroid  adminis- 
tration later.  Again,  extract  of  prostate  is  highly 
toxic;  and  if  prescribed  it  is  essential  that  the  initial 
dose  should  be  small,  and  its  reactions  carefully 
watched.  Likewise,  the  extracts  of  adrenals  and  pitui- 
tary glands  require  judicious  dosage,  and  cannot  be 
prescribed  in  a  haphazard  manner. 

On  the  other  hand,  the  preparations  of  such  organs 


282   THE  ORGANS  OF  INTERNAL  SECRETION 

as  the  liver,  spleen,  pancreas,  testicle,*  ovary,  etc.,  are 
in  no  way  poisonous,  and  large  doses  can  be  given 
with  comparative  safety.  In  many  instances,  how- 
ever, the  administration  of  these  latter  extracts  par- 
takes of  empirical  therapy,  for,  frequently,  the  deci- 
sion to  endeavour  to  remedy  certain  symptoms  rests 
more  on  a  supposed  deficiency  than  upon  definite 
signs  of  inadequacy  of  a  particular  gland.  Thus,  in 
cases  where  intestinal  stasis  appears  to  be  present,  it 
may  be  assumed  that  this  depends  upon  a  deficiency 
of  one  of  the  alimentary  secretions,  to  remedy  which 
we  prescribe  a  preparation  of  the  gland  in  question. 
This,  although  empirical,  has  much  to  recommend  it, 
and  is  surely  preferable  to  constant  dosing  with  purga- 
tives, accompanied,  as  such  treatment  always  is,  by 
unpleasant  sequelae. 

Another  aspect  of  organo -therapeutic  dosage  has 
been  defined  by  Hallion,  and  concerns  itself  with  the 
stimulant  action  of  an  extract,  administered  to  man 
or  animal,  on  the  organ  secreting  that  extract.  "  Ex- 
tracts of  an  organ  exert  on  the  same  organ  an  exciting 
influence,  which  lasts  for  a  longer  or  shorter  time. 
When  the  organ  is  insufficient,  it  is  conceivable  that 
this  influence  augments  its  action,  and,  when  it  is 
injured,  that  it  favours  its  restoration."  It  is  here 
assumed  that,  so  long  as  a  part  of  a  gland  remains 
unaffected,  it  is  possible  to  regenerate  it  from  the 
secreting  point  of  view,  so  that  administration  of  its 
extract  will  have  more  than  a  temporary  influence. 

*  See  footnote  to  p.  198. 


APPLICATION  OF  HOEMONES  283 

Again,  even  supposing  that  the  gland  is  absent  or 
totally  destroyed,  the  administration  of  its  extract 
will,  in  some  instances — e.g.,  thyroid — replace  the 
natural  secretion. 

Still  another  aspect  of  the  treatment  by  extracts  of 
the  endocrinic  glands  is  what  may  be  termed  "  antago- 
nistic action."  By  this  we  mean  the  power  of  neutral- 
izing an  excessive  secretion  of  one  gland  by  the 
exhibition  of  an  extract  of  another,  assumed  to  be 
antagonistic.  This  adjustment  of  secretions  in  order 
to  obtain  the  hormone  balance  is  one  of  the  most 
important  features  of  organo- therapeutics,  and  in  all 
probability  the  future  will  see  its  utility  widely  ex- 
tended. In  the  past,  as  is  well  known,  when  Graves' 
disease  was  supposed  to  depend  primarily  upon  an 
excess  of  thyroid  secretion,  treatment  by  means  of 
adrenal  administration  was  much  vaunted,  especially 
by  the  late  Dr.  Gibson,  who  spoke  very  highly  of  the 
results  accruing  therefrom. 

There  is  also,  in  addition  to  the  uses  already  men- 
tioned, the  physiological  administration  of  organic 
extracts.  As  an  example  of  this  method  we  may  cite 
the  obstetrical  use  of  hypophyseal  extract  to  promote 
uterine  contraction,  and  the  prescribing  of  the  same 
substance  to  counteract  shock.  These  uses  belong  to 
the  class  referred  to  by  Starling  as  "  acute,"  only 
in  the  therapeutic  sense.  Starling,  by  his  division 
of  the  hormones  into  acute  and  chronic,  referred  to 
those  hormones  which  under  physiological  stimulus 
secrete  suddenly  an  increased  amount  of  a  particular 


284  THE  ORGANS  OF  INTERNAL  SECRETION 

hormone — e.g.,  the  pouring  into  the  blood  of  adren- 
alin under  the  stimulus  of  fright,  and  the  constant 
supply  of  thyroid  for  metabolic  purposes,  respec- 
tively. 

It  will  be  seen  from  this  brief  survey  of  the  rationale 
of  hormone- therapy  that  its  uses  are  many,  and  that 
its  application  is  logical.  It  is  obvious  that  at  present 
we  are  only  on  the  fringe  of  the  possibilities  of  such 
treatment,  and  that  the  near  future  will  see  its  develop- 
ment to  an  immense  degree.  We  do  not  mean  that 
the  empirical  and  sometimes  illogical  dosing  by 
organic  extracts,  or  the  exhibition  of  every  extract  of 
the  human  body  in  the  vain  hope  of  "  hitting  the 
target  somewhere,"  will  be,  or,  for  the  matter  of  that, 
ought  to  be,  widely  developed.  What  we  infer  is 
that,  with  increased  knowledge  of  the  functions  of  the 
endocrinic  organs  and  their  relations  to  each  other, 
fresh  fields  of  scientific  prescribing  will  be  open  for 
use,  and  that  many  of  the  cases  which  we  now  treat 
with  inorganic  medicines,  in  the  blind  hope  that  Nature 
will  step  in  and  cure  while  we  are  gaining  time, 
will  be  positively  treated  by  organic  extracts,  with 
the  almost  certain  knowledge  that  definite  symptoms 
will  disappear,  and  that  normal  features  will  re- 
appear. 

We  will  now  consider  the  uses  to  which  these  extracts 
may  be  put  in  practice,  and  we  will  commence  with 
the  extract  of  thyroid. 

In  a  previous  chapter  we  dealt  with  the  methods 
of  prescribing  thyroid  extract  for  myxcedema  and  sub- 


APPLICATION  OF  HORMONES  285 

myxoedema,  and  described  the  dosage.  We  will  deal 
here  with  other  uses  to  which  this  extract  can  be  put, 
but  must  say  at  once  that  many  of  these  are  founded 
on  empirical  reasoning. 

For  some  years  the  nocturnal  enuresis  from  which 
so  many  children  suffer  has  been  treated  with  thyroid 
extract,  and,  in  many  instances,  with  striking  success. 
Not  all  these  cases,  it  is  needless  to  say,  suffer  from 
thyroid  inadequacy,  but  many  of  them  doubtless  do  so 
suffer,  and  the  increased  thyroid  content  of  the  blood 
effectually  helps  to  check  this  enuresis.  As  Hertoghe 
has  pointed  out,  a  condition  of  thyroid  deficiency 
nearly  always  produces  frequency  of  micturition, 
owing  to  the  poor  nutrition  of  the  walls  of  the  bladder, 
which,  in  consequence,  desquamate  rapidly,  rendering 
the  bladder  unduly  sensitive  to  stimuli.  In  such 
cases  thyroid  extract  is  urgently  needed;  and  unless 
it  is  supplied  in  increasing  doses  from  within,  or  the 
internal  supply  augmented  from  without,  it  is  diffi- 
cult to  see  how  the  symptoms  arising  therefrom  can 
be  remedied. 

This,  then,  is  one  of  the  uses  to  which  this  extract 
can  be  put,  and  another  use  is  connected  with  this, 
inasmuch  as  the  condition  is  frequently  found  asso- 
ciated with  enuresis,  obviously  because  the  causation 
is  identical.  We  refer  to  adenoids  and  enlarged  tonsils. 
Hertoghe  has  rendered  an  inestimable  service  to 
medicine  by  explaining  the  underlying  pathology  of 
these  cases.  He  emphasizes  the  induration  and  thick- 
ening which  is  always  present  where  the  thyroid  secre- 


286   THE  OKGANS  OF  INTERNAL  SECRETION 

tion  is  deficient;  not  only  in  the  subcutaneous  tissue, 
but  in  places  where  formerly  its  existence  had  scarcely 
been  suspected.  Thus,  the  tinnitus  aurium  and  deaf- 
ness of  subthyroidics  may  be  assumed  to  be  due  to 
infiltration  of  the  aural  passages  and  apparatus;  the 
growth  of  adenoids  to  the  same  cause;  the  headaches 
and  nervous  symptoms  to  neural  infiltration ;  and 
the  enlargements  of  the  tonsils  to  fibrous  hyper- 
plasia. 

These,  which  are  only  a  few  examples,  will  serve  to 
indicate  the  lines  along  which  thyroid-therapy  can  be 
conducted.  If,  therefore,  a  child  exhibits  one  or  more 
of  these  symptoms,  confirmatory  evidence  should  be 
looked  for.  The  subject  of  nocturnal  enuresis  may 
show  the  presence  of  adenoids,  may  have  enlarged 
tonsils,  or  exhibit  other  signs  of  thyroid  deficiency. 
The  "  adenoid  facies  " — i.e.,  the  mental  condition  plus 
the  physical  conformation  of  countenance — would  be 
much  more  correctly  described  as  the  "  subthyroidic 
facies."  This  being  so,  it  will  be  obvious  that  such  a 
child  owes  urinary  symptoms  of  this  nature  to  defici- 
ency of  thyroid,  and  not  to  local  conditions  per  se  ; 
but  we  must  emphasize  in  passing  the  importance  of 
excludmg  certain  local  factors,  such  as  calculus  and 
phimosis.  Fascinating  as  this  form  of  treatment  is, 
and  almost  limitless  as  the  vista  of  healing  is  which 
is  opened  by  its  conception,  diagnosis  must  always 
precede  treatment. 

For  these  patients  a  small  dose  of  thyroid,  increased 
gradually  as  is  required,  is  indicated.     The  initial  dose 


APPLICATION  OF  HOEMONES  287 

should  be  a  fraction  of  a  grain,  according  to  the  age 
of  the  patient.  Thus,  one-sixth  to  one- quarter  of  the 
dry  extract  or  a  minim  or  two  of  the  liquor  thyroidei 
is  enough  to  commence  with,  and  a  careful  watch  is 
essential  to  ascertain  the  reaction  of  the  system  to  the 
extract. 

Again,  obese  patients  should  be  examined  for  signs 
of  thyroid  inadequacy,  as  where  such  increase  in  weight 
is  of  recent  occurrence  the  treatment  should  immedi- 
ately be  instituted — the  sooner  the  better — once  the 
diagnosis  has  been  made.  Even  if  the  signs  of  thyroid 
deficiency  are  of  long  duration,  the  prognosis  is  equally, 
or  almost  equally,  good;  for  although  the  treatment 
must  be  spread  over  a  much  longer  time,  nevertheless 
the  benefit  accruing  is  usually  great. 

Some  of  these  cases  are  not  solely  due  to  thyroid 
inadequacy,  but  are  a  mixture  of  thyroid  and  pituitary 
deficiency.  It  is  a  little  difficult  to  describe  the  diag- 
nostic features  in  a  few  words,  but  the  indications  of 
thyroid  inadequacy  are  a  slow  pulse,  dry  and  rough 
skin,  subnormal  temperature,  and  obesity;  while  the 
signs  of  hypophyseal  deficiency  are  an  increase  in 
weight,  a  smooth  skin — as  opposed  to  the  rough  skin 
of  submyxcedema — a  low  blood- pressure,  and  a  dis- 
turbance of  function,  as  exemplified  by  constipation, 
with  often  a  marked  degree  of  meteorism  and  faulty 
digestion. 

For  such  cases  thyroid  should  be  prescribed,  and 
when  the  dose  has  reached  what  may  be  regarded  as 
sufficient  for  the  individual  case,  but  still  symptoms 


288    THE  OEGANS  OF  INTEKNAL  SECBETION 

remain  which  do  not  improve,  then  pituitary  extract 
may  be  added  to  the  thyroid.  Such  a  procedure  will 
often  help  where  thyroid  by  itself  fails;  and,  provided 
the  dose  of  both  substances  is  regulated  to  the  indi- 
vidual case  and  not  by  rule  of  thumb,  no  ill  results 
should  accrue. 

If,  in  patients  of  this  type,  no  benefit  results  from 
the  combination  of  thyroid  and  pituitary  extract,  it 
will  often  be  found  that  the  addition  of  a  small  dose 
of  extract  of  the  gonads  will  be  of  great  help.  This  is 
not  "  a  shot  in  the  dark,"  neither  is  it  trying  every 
hormone  in  turn;  but,  in  the  present  writer's  experi- 
ence, cases  of  this  nature  frequently  respond  to  a  com- 
bined extract  when  they  fail  to  improve  on  one  product. 
This  is  presumably  because,  whatever  the  original 
glandular  defect  has  been,  disturbances  of  the  endo- 
crine balance  have  been  established  by  the  time  the 
patient  comes  under  notice. 

We  shall  not  discuss  this  subject  at  greater  length 
here,  but  further  reference  to  it  will  be  found  in 
Chapter  IX. 

The  preparations  of  thyroid  which  may  be  utilized 
have  already  been  mentioned,  but  in  order  that  this 
chapter  may  be  helpful  in  actual  practice,  we  will 
enumerate  them  once  more. 

The  total  extract  of  thyroid  may  be  given,  or  the 
dry  extract  chosen,  if  preferred;  one  part  of  the  dry 
extract  is  approximately  equivalent  to  five  parts  of 
the  other  extract.  The  dose  of  extracts  should  be 
minimal  to  commence  with,  and  opinions  vary  as  to 


APPLICATION  OF  HORMONES  289 

the  margin  of  safety.     So  far  as  the  experience  of  the 
present  writer  is  concerned,  one-half  to  one  grain  of 
the  total  extract  three  times  a  day  is  a  good  dose  to 
commence  with,  and  can  be  increased  with  due  observ- 
ance of  the  alteration  in  weight,  pulse- rate,  and  blood- 
pressure.     Again,  if  a  liquid  preparation  be  preferred, 
liquor  thyroidei,  in  doses  of  from  a  few  minims  to  about 
seven  or  eight,  is  a  satisfactory  method  of  administer- 
ing this   extract,  provided  that  the  preparation  be 
fresh.     Elixir  Colloid  (Squire)  presents  this  gland  in  a 
palatable  form,  and  it  can  be  combined  with  a  pituitary 
extract  if  desired.     The  same  firm  manufactures   a 
liquid  preparation  of  the  pituitary  gland,  under  the 
name  of  Elixir  Hypophysis  Cerebri,  with  a  dose  which 
may  range  from  a  few  minims  to  two  drachms.     These 
preparations  are  a  convenient  way  to  admimster  the 
thyroid  and  pituitary  glands  to  the  same  patient  at 
the  same  time,  and  the  relative  doses  may  be  regulated 
with  ease. 

The  hypophysis  may  be  given  in  tablets,  and  several 
firms  manufacture  this  extract  either  by  itself  or  in 
conjunction  with  other  extracts.  Or,  again,  capsules 
of  this  gland  are  put  up,  either  as  single  products  or 
in  combination  with  other  organic  extracts,  by  the 
British  Organo-therapy  Company.  These  preparations 
are  coated  in  soluble  gelatine,  air-tight  covers,  and  are 
thus,  it  is  claimed,  less  liable  to  deterioration.  This 
firm  manufactures  capsules  of  the  whole  pituitary 
gland,  or  of  the  anterior  lobe  only.  Injections  of  the 
posterior  lobe  of  the  pituitary  are  manufactured  by 

19 


290    THE  OEGANS  OF  INTERNAL  SECRETION 

this  firm,  conveyed  in  physiological  salt  solution.  We 
are  not  so  much  concerned  here  with  the  urgent  use  of 
these  extracts,  as  exemplified  by  their  utilization  in 
shock,  obstetrical  emergencies,  and  surgical  cases,  and 
we  shall  therefore  pass  over  the  employment  of 
adrenalin,  pituitarin,  and  other  preparations  of  these 
glands  for  their  immediate  action,  and  deal  with  their 
use  from  the  routine  standpoint  only. 

The  extract  of  the  adrenal  gland  has  definite  and 
powerful  properties,  and,  if  used,  requires  great  care 
in  its  administration.  As  it  raises  the  blood- pressure 
and  causes  a  rapid  rise  in  the  pulse-rate,  it  should 
never  be  given  in  cases  of  arterio-sclerosis,  or  in  hyper- 
piesis  where  there  has  been  haemoptysis,  or  in  glycosuria. 
In  fact,  its  prolonged  administration  is  not  desirable, 
except  with  great  care,  and,  considering  that  extract  of 
the  pituitary  is  much  less  toxic,  and  that  the  results  are 
almost  as  favourable,  the  administration  of  adrenal 
extract  has  not  become  popular. 

There  are,  however,  certain  patients  in  whom  the 
indications  for  adrenal  therapy  are  plain.  To  take  one 
example,  the  case  of  chronic  exhaustion,  the  patient 
who  is  always  tired,  who  complains  of  muscular 
tremors  upon  the  slightest  exertion,  is,  I  think  most 
clinicians  will  agree,  a  most  difficult  therapeutic 
problem.  While  the  etiology  of  such  a  condition  is 
often  obscure,  it  may  well  be  that  adrenal  exhaustion 
is  the  cause  of  the  present  symptoms.  Examination 
will  reveal  a  low  blood- pressure  at  one  time,  a  normal 
reading  at   the^next.     But  the  ready  fatigability  is 


APPLICATION  OF  HORMONES  291 

beyond  dispute,  and  is  certainly  not  always  psycho- 
genic. 

I  have  utilized  adrenal  extracts  for  this  condition, 
both  orally  and  by  the  hypodermic  or  intramuscular 
method.*  Their  employment  requires  care,  as  we 
have  said,  and  small  doses  should  be  administered  to 
commence  with,  and  gradually  increased  until  a  full 
dose  is  reached.  The  contra-indications  have  already 
been  discussed. 

Extracts  of  the  gonads,  which  are  sometimes  manu- 
factured in  combination  with  extracts  of  the  central 
nervous  system,  will  be  found  to  have  a  wide  applica- 
bility. Thus,  in  neurasthenic  cases,  in  patients  who 
are  run  down,  and  in  delayed  convalescence,  they  are 
frequently  of  the  greatest  use.  As  Brown- Sequard  was 
the  first  to  show  with  reference  to  testicular  extract, 
they  increase  the  capacity  for  muscular  work,  revive 
the  tired  nervous  system,  and  have  a  general  "  tonic  " 
influence  upon  the  functions.  The  present  writer  has 
utilized  them  for  several  different  types  of  disease  (or 
perhaps  the  word  "  disorder  "  is  more  suitable),  such 
cases  ranging  from  marasmic  wasting  to  impotence. 
It  is  a  little  difficult  to  give  definite  indications  for 
their  use,  and  perhaps  it  will  be  better  to  cite  one  or 
more  cases  in  which  their  use  at  the  hands  of  the  present 
writer  has  been  attended  with  success.  One  was  a 
man  aged  thirty,  with  rapid  wasting  and  low  blood- 

*  See  Chapter  VII.,  p.  168,  for  note  on  the  rectal  adminis- 
tration of  adrenalin.  Also  see  section,  p.  162,  for  discussion  on 
hypo-adrenia. 


292   THE  ORGANS  OF  INTERNAL  SECRETION 

pressure,  who  had  been  in  a  very  depressed  mental 
condition  for  over  two  years.  His  treatment  con- 
sisted, inter  alia,  in  rest  in  bed  for  six  weeks,  with 
hyper- alimentation  and  this  form  of  organo- thera- 
peutic treatment.  At  the  end  of  a  month  his  weight 
had  increased  by  over  one  stone,  and  his  improvement 
in  every  way  was  most  striking.  By  the  end  of  six 
weeks  there  was  a  continuance  of  this  improvement, 
and  when  he  left  the  nursing  home  his  weight  had 
increased  by  a  total  of  two  and  a  half  stone,  his 
mentality  was,  for  all  intents  and  purposes,  normal, 
and  his  physical  health  quite  restored. 

Another  instance  of  the  same  treatment  was  in  a 
man  of  middle  age,  prematurely  old,  with  impotence, 
neurasthenia,  hypopiesis,  and  depression.  One 
month's  treatment  by  these  methods  restored  him  to 
normal,  raised  his  blood- pressure,  and  restored  his 
nervous  functioning.  In  this  case,  moreover,  there 
was  a  flabby  condition  of  the  genitals,  a  loss  of  sexual 
power,  and  a  diminution  of  testicular  sensation. 

A  preparation  called  "  spermin,"  isolated  by  Von 
Poehl,  and  believed  to  benefit  a  number  of  conditions, 
most  of  which  emanate  from  auto-intoxication,  has 
been  tried  with  some  success.  It  has  also  been  sug- 
gested that  extracts  of  the  gonads  are  useful  in  raising 
the  resistance  of  the  body  to  infection;  there  can  be 
little  doubt  that  they  are  valuable  in  "  revivifying  " 
the  overworked  organism. 

In  dealing  with  the  hormones  which  may  be  supplied 
from  animals,  we  must  refer  to  those  emanating  from 


APPLICATION  OF  HORMONES  293 

the  alimentary  canal  and  the  abdominal  organs. 
Thns,  we  encounter  "  secretin,"  which  was  isolated  by- 
Starling  from  the  duodenal  mucous  membrane.  In 
normal  health  this  substance  is  set  free  from  this 
mucous  membrane  as  soon  as  the  acid  chyme  enters 
the  bowel.  It  is  difficult  to  prescribe,  for  it  appears 
to  be  destroyed  when  given  by  the  mouth.  Neverthe- 
less, there  have  been  some  good  results  published, 
notably  by  Harrower,  and  this  should  encourage  its 
farther  trial.  As  this  hormone  is  a  direct  stimulant 
to  the  pancreatic  juice,  its  absence  or  diminution  must 
be  attended  with  some  degree  of  deficient  metabolism. 
A  manufacturer's  preparation  known  as  "  secretogen  " 
is  on  the  market,  and  the  present  writer  has  employed 
this  with  some  benefit. 

Again,  Zuelzer,  experimenting  to  ascertain  some 
substance  which  would  have  a  decided  action  in  in- 
creasing peristalsis,  discovered  a  hormone,  prepared 
from  the  gastric  and  duodenal  mucous  membrane, 
which  showed  this  property.  He  considers  that  this 
hormone  is  produced  in  the  stomach  and  duodenum, 
carried  off  in  the  blood,  and  stored  in  the  spleen.  A 
preparation  known  as  "  hormonal  "  was  then  manu- 
factured, mainly  from  the  spleen  of  animals,  and 
administered  with  or  without  pituitarin.  Apart  from 
cases  of  spastic  constipation  and  the  like,  this  is,  as 
Harrower  points  out,  a  useful  remedy  for  deficient 
peristalsis. 

As  there  was  some  danger  from  the  use  of  hormonal, 
which  was  apparently  due  to  the  presence  of  an  albu- 


294  THE  OEGANS  OF  INTERNAL  SECRETION 

mose,  this  remedy  has  now  been  discontinued,  and  a 
fresh  substance,  with  the  harmful  constituent  removed, 
has  been  placed  on  the  market,  and  the  results  quoted 
in  Harrower's  book  speak  very  highly  of  its  action, 
more  especially  in  cases  of  intestinal  paresis.* 

Another  combination  of  an  internal  secretion  with 
the  external  secretion  is  to  be  found  in  "trypsogen," 
which  contains  the  pancreatic  secretion  and  ferments. 
This  is  recommended  for  use  in  cases  of  diabetes,  or 
where  it  may  be  presumed  that  the  pancreas  is  at 
fault.  Another  use  for  the  same  preparation  is  in 
hypertension,  but  there  are  other  methods  of  treating 
this  condition,  which  must  only  receive  organo- 
therapeutic  treatment  of  any  kind  when  its  origin  has 
been  determined. 

We  will  pass  over  the  administration  of  bile-salts  as 
a  rational  laxative,  as  the  subject  is  too  large  to  admit 
of  adequate  treatment  in  a  chapter  of  this  length. 
Suffice  it  to  say  here  that  bile-salts  are  clearly  indi- 
cated in  some  cases  of  constipation,  more  particularly 
where  there  is  reason  to  suspect  a  disordered  liver, 
with  deranged  bile  secretion  into  the  bowel.  A  few 
grains  of  bile-salts,  about  three  to  five,  form  an  excel- 
lent laxative,  while  in  larger  doses  such  an  extract  is 
cathartic. 

Before  concluding  this  rapid  survey  of  hormonic 
preparations,  we  must  refer  to  the  less  definite  internal 
secretions  and  their  administration.  Of  these,  ovarian 
extract,  either  whole  extract  or  else  extract  of  the 

*  This  preparation  has  received  the  name  "  neo-hormonal." 


APPLICATION  OF  HOEMONES  295 

corpus  luteum,  has  been  given  in  a  variety  of  con- 
ditions, either  alone  or  with  one  of  the  other  endocrine 
preparations.  It  has  been  found  useful  in  disorders 
of  the  catamenia,  at  the  climacteric,  for  post-operative 
disorders,  such  as  those  which  follow  double  oophorec- 
tomy, and  as  an  antagonist  to  certain  of  the  other 
internal  secretions.  In  similar  manner,  the  extract 
of  the  mammary  gland  finds  a  field  of  utility,  and 
has  been  prescribed  for  uterine  conditions  (it  will  be 
remembered  that  there  is  a  close  connection  between 
the  uterus  and  the  mammae)  and  as  a  galactogogue. 
Some  observers  speak  highly  of  its  efficacy  in  this 
connection. 

We  have  already  mentioned  the  use  of  prostatic 
extract,  and  stated  that  it  is  a  toxic  substance,  and 
therefore  of  limited  utility.  The  present  writer  has 
had  insufficient  experience  of  this  extract  to  speak 
definitely;  but  it  is  stated  to  be  useful  in  controlling 
the  peculiar  melancholic  condition  which  sometimes 
supervenes  after  removal  of  the  prostate. 

General  Survey  of  Organo-Therapy. 

We  will  now  briefly  recapitulate  what  we  have  said 
with  reference  to  the  uses  of  organic  extracts  in  medi- 
cine, and  amplify  our  remarks  by  quoting  some  typical 
cases  in  which  its  administration  has  proved  beneficial. 
As  we  have  arranged  this  book  so  that  a  brief  summary 
of  treatment  will  be  found  at  the  end  of  each  chapter, 
it  may  be  convenient  to  summarize  our  conclusions  in 


296    THE  ORGANS  OF  INTERNAL  SECRETION 

one  chapter,  so  that,  if  desired,  the  therapeutics  dealt 
with  in  this  volume  may  be  gleaned  from  a  perusal  of 
this  chapter. 

Organo- therapy  holds  out  the  hope  that  it  will 
ameliorate  the  unhappy  lot  of  many  patients  suffering 
from  diseases  which  have  hitherto  been  intractable  to 
most  forms  of  treatment.  It  has  been  welcomed  with 
open  arms;  its  component  extracts  have  been  pre- 
scribed in  many  maladies,  and  the  reports  as  to  the 
results  of  this  medication  have  been  various  and 
frequently  contradictory.  So  far  as  the  lesser-known 
organic  preparations  are  concerned,  this  book  has  not 
had  the  requisite  space  to  deal  with  them;  neither  do 
they  seem,  if  we  may  say  so,  to  come  within  the  scope 
of  a  work  such  as  this. 

The  author  has  endeavoured  to  describe  the  grosser 
lesions  in  which  organic  preparations  may  be  employed 
with  a  prospect  of  success,  and  he  has  attempted  to 
outline  morbid  conditions  in  which  such  extracts  can 
be  prescribed.  It  must  be  remembered  that  an 
organic  preparation  may  be  used  in  several  ways;  thus, 
it  may  be  given  to  replace  the  same  secretion,  which 
is  assumed  to  be  deficient  (substitution  therapy);  it 
may  be  administered  to  increase  a  secretion  which  is 
presumably  not  supplied  by  the  gland  in  sufficient 
quantity;  it  may  be  prescribed  in  the  hope  of  antag- 
onizing the  excessive  secretion  of  one  or  more  of  the 
other  internal  secretory  glands;  or  it  may  be  given 
purely  for  its  physiological  action. 

A  vast  range  of  utility  is  thus  opened  for  prepara- 


APPLICATION  OF  HORMONES  297 

tions  of  the  organic  extracts;  and  now  that  the  signs 
and  symptoms  of  deranged  secretion  are  more  widely- 
known,  the  application  of  the  theoretical  knowledge 
of  the  endocrine  glands  to  actual  therapeutic  practice 
is  becoming  easier  than  when  such  prescribing  was 
almost  solely  empirical.  As  an  example,  the  many 
different  abnormalities  which  thyroid  extract  will 
correct,  in  one  or  other  of  its  applications,  are  daily 
receiving  additions,  as  we  discover  fresh  symptoms  of 
thyroid  insufficiency. 

Originally  its  therapeutic  use  was  confined  to  the 
treatment  of  myxcedema.  When  this  disease  was 
seen  to  be  remedied  by  thyroid  feeding,  a  mild  type 
of  the  same  disease  was  recognized  as  yielding  to  the 
persuasive  powers  of  this  extract.  Submyxoedema  as 
a  clinical  entity  has  been  supplemented  by  a  variety 
of  symptoms,  any  one  of  which,  when  present,  may 
sometimes  be  ascribed  to  hypothyroidism.  Thus,  we 
may  say  that  a  consistently  slow  pulse  points  to  a 
deficiency  in  the  thyroid  output,  although  other 
symptoms  must  necessarily  be  present  before  we  can 
diagnose  "submyxoedema."  But  it  does  not  follow, 
of  course,  that  every  person  with  a  slow  pulse  has 
hypothyroidism,  although,  by  the  physiological  use  of 
this  extract,  it  might  be  justifiable  to  accelerate  this 
slow  pulse-rate,  were  it  desirable,  by  the  judicious 
administration  of  thyroid. 

Again,  any  of  the  symptoms  which  are  so  well 
recognized  when  grouped  together  in  the  same  patient, 
as  pointing  to  the  thyroid  as  the  organ  at  fault,  may 


298   THE  OEGANS  OF  INTERNAL  SECKETION 

be  treated  by  means  of  this  extract,  provided  that  a 
careful  watch  is  kept  of  the  reaction  of  the  patient  to 
this  remedy. 

A  few  examples  will  explain  how  this  principle  may 
be  applied  to  practice. 

Case  1. — M.  W.,  est  33,  married,  with  one  child. 
Shortly  after  she  became  pregnant  (three  years  before 
the  date  she  first  consulted  me),  she  noticed  she  was 
feeling  better  in  her  general  health  than  she  had  done 
for  some  years,  as  she  had  previously  suffered  from 
indigestion  and  constipation,  and  her  "  nerves  had 
been  bad."  She  informed  me  that  shortly  after  her 
child  was  born  she  relapsed,  and  that  about  this  time 
brown  patches  appeared  upon  her  face.  These  had 
continued  ever  since,  and  her  health  had  never  been 
restored  to  normal. 

On  examination^  very  marked  patches  of  a  light 
brown  colour  were  seen  on  the  forehead  and  around 
the  mouth.  These  were  so  marked  as  to  cover  nearly 
the  whole  forehead,  although  there  were  clear  areas  of 
normal  skin  between.  Her  pulse  was  slow,  although 
not  markedly  so,  and  the  thyroid  gland  was  prominent, 
the  neck  measuring  13J  inches  at  the  level  of  this 
gland.  She  was  quite  abnormally  sleepy,  and  became 
unduly  tired. 

I  prescribed  one  half- grain  tablet  of  thyroid  gland 
daily,  to  be  increased  in  a  week  to  one  grain  in  the 
day.  This  was  gradually  increased  until  she  was 
taking  three  one- grain  tablets  daily. 

The    result    was    most    gratifying.     Three    months 


APPLICATION  OF  HORMONES  299 

from  the  commencement  of  treatment  the  patches  had 
almost  disappeared,  and  small  areas  only  of  slightly 
darker  colour  than  the  surrounding  skin  could  be  seen 
in  a  good  light.  She  stated  that  her  general  health 
was  much  better,  and  she  remarked  that  "  she  felt 
fitter  than  she  had  since  her  baby  was  born."  The 
thyroid  had  decreased  in  size,  and  the  neck  measure- 
ment was  barely  13  inches. 

Note. — This  case  is  instructive  for  the  following 
reasons : 

1.  The  thyroid  secretion  had  evidently  increased 
during  pregnancy,  when  she  experienced  better  health, 
but  had  diminished  after  parturition,  which  is  often 
the  case. 

2.  The  patches  of  pigmentation  yielded  promptly  to 
the  ingestion  of  thyroid. 

3.  The  general  health  improved  pari  passu,  both 
the  digestion  and  the  bowels  functioning  more  nor- 
mally. 

4.  The  decrease  in  the  thyroid  gland  under  this 
treatment  pointed  to  the  swelling  as  a  hypertrophy  of 
the  gland,  an  effort  to  increase  the  deficient  secretion. 

Case  2. — J.  W.,  cd.  47,  complained  of  an  increasing 
weight,  accompanied  by  dyspnoea  on  exertion,  broken 
sleep,  digestive  disturbances,  and  constipation.  This 
condition  had  been  of  gradual  onset,  but  had  been 
rapidly  increasing  of  late. 

On  examination,  the  increase  of  weight  was  largely 
accounted  for  by  deposits  of  fat  in  the  regions  of  the 
abdomen  and  shoulders;  the  pulse  was  about  70,  the 


300   THE  ORGANS  OF  INTERNAL  SECRETION 

temperature  subnormal,  the  blood- pressure  was  145 
mm.  Hg,  and  the  urine  contained  large  quantities 
of  phosphates.  The  skin  was  dry  and  rather 
rough,  and  the  patient  most  markedly  bald;  this 
latter  feature  he  had  treated  by  the  adoption  of 
a  wig. 

I  restricted  his  carbohydrate  food,  ordered  an  occa- 
sional saline,  and  commenced  with  small  doses  of 
thyroid.  In  a  month's  time  he  had  lost  9  pounds,  and 
felt  and  looked  better.  His  digestion  improved,  his 
sleep  became  more  normal,  and  his  energy  returned. 
This  is  a  year  ago,  and  he  still  remains  in  good  health, 
although  a  relapse  in  weight  occasioned  a  fresh  course 
of  thyroid  medication. 

Case  3. — An  analogous  instance  is  the  case  of  Dr.  A. 
This  gentleman  consulted  me  for  similar  symptoms, 
but  certain  points  in  his  case  were  different.  Thus, 
his  inertia  was  greater,  fatigue  on  exertion  was  most 
marked,  his  blood- pressure  was  lower,  and  his  general 
syndrome  seemed  to  me  to  point  to  a  pluriglandular 
deficiency. 

He  took,  at  my  suggestion,  small  doses  of  thyroid 
combined  with  dry  extract  of  the  adrenals.  He  im- 
proved markedly,  but  had  to  continue  the  medication 
at  intervals  in  order  to  avoid  a  recurrence  of  the 
symptoms. 

Note. — Both  the  above  instances  presented  neuras- 
thenoid  symptoms,  but  the  improvement  in  each  case 
will  afford  evidence  that  many  so-called  "  neuras- 
thenics '    are  in  reality  sufferers   from  a  disturbed 


APPLICATION  OF  HOEMONES  301 

hormone  balance,  and  in  consequence  may  be  helped 
by  this  form  of  treatment.* 

Case  4. — M.  P.,  cet.  34,  complained  of  undue  fatigue, 
of  feeling  very  unwell  each  morning  on  waking,  and 
of  a  "  quite  extraordinary  tendency  to  fatigue."  He 
informed  me  that  he  had  "  always  had  a  very  slow 
pulse,  as  his  father  had  before  him."  This  was  cer- 
tainly true,  as  his  pulse-rate  at  the  first  consultation 
was  about  50  per  minute.  His  blood-pressure  was 
low,  his  temperature  subnormal,  but  his  weight  was 
about  normal  for  his  height. 

There  is  little  further  need  to  discuss  this  case,  for 
the  diagnosis  was  obvious.  His  symptoms  all  yielded 
to  the  administration  of  thyroid  extract,  which  in- 
creased appetite,  regulated  sleep,  and  approximated  the 
pulse-rate  to  normal,  so  that  his  circulation  improved 
and  he  was  able  to  resume  his  normal  life,  which 
entailed  a  considerable  amount  of  active  exercise. 

Case  5. — An  interesting  case  came  under  my  notice 
some  time  ago.  A  young  girl  was  brought  to  me  whose 
mental  development  was  deficient,  although  physi- 
cally she  was  quite  normal,  with  the  exception  of  a 
markedly  protuberant  abdomen.  In  this  case,  as 
growth  proceeded,  she  had  exhibited  signs  of  a  lack 
of  mental  development,  and  an  eminent  surgeon  had 
decided  to  operate,  and  implant  a  thyroid  graft  in  the 
hope  that  the  thyroid  secretion  would  replace  the 
hypothyroidism  which  was  assumed  to  exist. 

When  I  saw  this  patient  it  was  five  years  since  the 

*  For  further  remarks  on  the  psycho-neuroses  see  Chapter  XII. 


302   THE  OEGANS  OF  INTERNAL  SECRETION 

operation,  and  the  main  features  of  the  case  were  as 
follows : 

Her  stature  was  decidedly  above  the  average,  and 
her  weight  over  12  stone.  She  was  fully  developed 
physically,  but  her  circulation  was  so  poor  that  she 
suffered  from  chilblains  on  the  hands,  feet,  and  legs. 
Her  pulse  was  slow,  about  48  per  minute,  her  tempera- 
ture markedly  subnormal,  her  blood- pressure  low,  but 
there  was  nothing  abnormal  in  the  heart.  In  the 
epigastrium  and  umbilical  regions  was  a  large  swell- 
ing, tympanitic  on  percussion,  which  displaced  the 
liver,  and  cardiac  dulness  upwards.  An  X-ray  exam- 
ination in  conjunction  with  a  bismuth  meal  had  failed 
to  locate  this.  The  skin  was  harsh,  dry,  and  scaly. 
The  bowels  were  regulated  by  means  of  liquid  paraffin. 
This  case  appeared  to  be  due  to  thyroid  deficiency, 
but  it  will  readily  appear  that  this  was  not  the  only 
secretion  at  fault.  The  patient's  father  came  of  a 
family  of  giants,  and  it  seemed  probable  that  there 
was  an  element  of  dyspituitarism  in  this  case;  that  is 
to  say,  that  the  patient  may  have  suffered  during  child- 
hood from  a  condition  of  unbalanced  pituitary  action 
which  had  been  followed  during  adolescence  by  hypo- 
pituitarism. 

Acting  upon  this  presumption,  I  prescribed  a  mixture 
containing  a  small  dose  of  thyroid  extract  and  a  large 
dose  of  pituitary.  The  improvement  has  been  marked, 
particularly  as  regards  the  circulation,  but  enough 
time  has  not  elapsed  to  enable  a  definite  result  to  be 
recorded.     The  abdominal  condition  is  slowly  improv- 


APPLICATION  OF  HOEMONES  303 

ing,  and  the  tympanitic  mass  is  responding  to  the 
stimulation  of  the  alimentary  canal  by  the  hypo- 
physeal extract.  This  swelling  I  assumed  to  be  a 
dilated  transverse  colon  which  was  consequent  upon 
the  deficient  innervation  of  the  bowel. 

Case  6. — W.  P.,  a  case  of  advanced  neurasthenia 
with  marked  loss  of  weight.  This  patient  suffered 
from  mental  depression  and  digestive  atony,  and 
accompanying  neurasthenic  symptoms. 

There  was  also  evidence  of  a  lowered  blood-pressure 
and  a  sluggish  cardiac  action.  Although  this  patient 
had  been  under  treatment  for  some  time  by  many 
different  methods,  no  improvement  had  taken  place. 
However,  a  short  course  of  treatment  by  a  pluri- 
glandular preparation  was  followed  by  a  disappear- 
ance of  nearly  all  the  abnormalities,  and  the  patient 
returned  to  his  home  and  resumed  his  normal  life, 
which  he  had  been  unable  to  do  for  three  years 
previously. 

Dr.  Gowing-Middleton,  of  Wymondham,  has  sent 
me  the  results  of  organo-therapeutic  treatment  in 
several  of  his  patients.  From  his  most  instructive 
account,  I  select  the  following  cases. 

The  first  is  a  case  of  melancholia,  occurring  in  a 
woman  aged  fifty  at  the  menopause.  This  patient 
suffered  from  post-partum  melancholia  sixteen  years 
ago,  and  was  then  under  treatment  for  about  two 
years.  The  family  history  is  a  bad  one:  the  whole  of 
her  family  being  "  neurotic,"  and  the  patient's  mother 
suffering  from  senile  dementia. 


304    THE  OEGANS  OF  INTERNAL  SECRETION 

This  attack  commenced  rather  suddenly,  at  the  time 
the  catamenia  should  have  occurred.  The  patient 
appeared  dazed,  and  did  not  recognize  her  own  son. 
The  change  in  the  mental  outlook  was  very  great 
and  very  pitiful,  as  previously  she  had  been  a  clever 
and  charming  woman.  From  this,  she  became  rest- 
less and  suspicious,  refused  food,  could  not  be  made 
to  sleep,  and  consequently  was  unable  to  be  left  alone. 
Her  pulse  was  extremely  soft,  but  the  blood- pressure 
was  unable  to  be  taken,  owing  to  her  mental  condition. 

"  Her  family  decided  that  she  must  be  placed  under 
certificate.  In  the  meantime  I  controlled  the  rest- 
lessness by  bromides  and  valerian.  But,  having  read 
your  book  carefully,  I  decided  that  the  best  chance 
of  doing  anything  for  this  patient  lay  in  prescribing 
thyroid  or  pluriglandular  extracts.  I  therefore 
decided  to  delay  the  removal  of  this  patient  to  an 
asylum  and  initiate  organo-therapeutic  treatment. 
I  gave  her  hormotone,  one  tablet  three  times  a  day. 
...  In  ten  days  the  patient  had  greatly  improved. 
She  recognized  her  children,  but  was  still  very  sus- 
picious, and  imagined  that  someone  was  plotting  to 
take  the  children  from  her.  She,  however,  began  to 
eat  better,  the  sleep  improved,  and  she  gave  less 
trouble.  I  now  .  .  .  increased  the  hormotone  to  four 
tablets  daily.  In  a  month  she  had  so  much  improved 
that  the  question  of  placing  her  under  care  was  quite 
settled,  for  it  was  no  longer  needful." 

The  last  reports  of  this  patient  state  that  she  is 
"  wonderfully  better." 


APPLICATION  OF  HOEMONBS  305 

Another  case  of  interest  is  sent  me  by  Dr.  Gowing- 
Middleton.  The  patient  was  a  boy,  aged  seven,  an 
obvious  cretin,  with  symptoms  of  nocturnal  enuresis, 
obstinate  constipation,  mouth- dribbling,  and  "  the 
vacant  stare  of  imbecility."  Both  testes  were  un- 
descended, and  the  abdomen  rather  large,  but  no 
other  signs  of  disease  beyond  the  curious  mental 
condition.  The  treatment  adopted  in  this  case  con- 
sisted of  a  tablet  containing  5  grains  of  thymus  gland, 
thrice  daily,  with  half  a  tablet  of  hormotone. 

In  ten  days  the  nocturnal  enuresis  had  quite  ceased, 
and  he  was  able  to  sleep  ten  hours  without  urinating, 
a  feat  he  had  never  previously  accomplished.  The 
thymus  extract  was  increased  to  four  tablets  daily. 
After  five  weeks  of  such  treatment,  the  improvement 
in  the  urination  had  continued,  both  testes  were  in 
the  scrotum,  but  the  constipation  was  still  trouble- 
some. The  mental  condition  had  also  distinctly 
improved. 

One  other  case  is  instructive.  The  patient  was  a 
young  lady,  suffering  from  abdominal  pains  of  great 
severity,  which  had  been  attributed  to  ovarian 
neuralgia,  and  for  which  she  had  undergone  an 
operation. 

After  some  years,  during  which  the  abdominal  pain 
and  constipation  continued,  her  mental  condition 
became  unsatisfactory,  and  she  developed  depression, 
amounting  almost  to  melancholia,  and  became  quite 
unable  to  undergo  even  the  slightest  exertion. 

At  this  stage,  when  practically  all  other  remedies 

20 


306   THE  OEGANS  OF  INTEENAL  SECRETION 

had  failed,  she  was  treated  by  secretogen.  After  about 
a  month's  treatment  her  general  condition  had  very 
markedly  improved,  she  could  eat  articles  of  food 
which  she  had  previously  been  unable  to,  and  her 
mental  condition  approximated  to  normal.  "  At  the 
end  of  seven  months  her  condition  is  most  satisfactory. 
She  has  gained  in  weight,  has  a  splendid  appetite,  the 
action  of  the  bowels  is  much  improved,  she  does  not 
complain  about  her  uterine  trouble,  and  her  pains  have 
largely  disappeared." 

The  above  cases  are  certainly  interesting  and  con- 
vincing. In  none  of  them  can  it  be  fairly  said  that 
we  are  relying  upon  the  post  hoc  ergo  propter  hoc  fallacy 
to  claim  a  cure.  For,  in  all  three,  the  facts  of  the 
cases  appear  to  show  that  until  the  new  remedy  was 
exhibited,  and  a  fresh  weight  thrown  into  one  side 
of  the  scales,  the  abnormal  conditions  present  were 
running  their  allotted  course. 

In  the  first  case,  time  alone  will  show  whether  the 
cure  is  permanent,  or  if  a  fresh  exacerbation  of  the 
symptoms  will  arise.  Dr.  Middleton's  second  case  is 
a  pleasing  example  of  how  directly  and  speedily 
thyroid  extract  will  revolutionize  the  psycho-physical 
apparatus  in  juvenile  myxoedema.  His  third  case  is 
a  good  example  of  the  help  which  organo-therapy  will 
sometimes  render  when  all  other  remedies  have  failed. 
From  this  standpoint  it  is  an  instructive  case,  and 
one  which  should  direct  our  attention  to  other  and 
similar  instances  of  chronic  illness,  where  help  may 
be  obtained  from  the  judicious  use  of  these  extracts. 


APPLICATION  OF  HORMONES  807 

The  cases  we  have  described  will  show  the  lines  upon 
which  treatment  by  the  more  important  organic 
extracts  may  be  regulated.  The  legitimate  uses  to 
which  thyroid  extracts  may  be  put  are  not  confined 
to  myxcedema,  or  even  definite  submyxcedema;  there 
are  a  number  of  symptoms,  sometimes  isolated,  which 
may  be  remedied  by  this  substance.  Case  1,  p.  298, 
will  show  that  one  symptom  will  often  point  the  way 
to  the  underlying  pathology. 

But,  as  was  seen  in  Cases  3  and  5,  the  full  benefit 
was  derived  by  a  combination  of  extracts — in  the 
former  by  the  association  of  thyroid  and  suprarenal 
extracts,  in  the  latter  by  that  of  thyroid  and  pituitary. 
It  is  not  always  easy  to  decide  on  the  particular  com- 
bination to  employ,  neither  can  definite  reasons  always 
be  given  for  the  choice.  But  if  the  signs  which  ac- 
company one  abnormality  appear  to  be  contradictory, 
either  the  preliminary  diagnosis  may  be  at  fault,  or 
else  more  than  the  one  gland  may  be  at  the  root  of  the 
trouble.  As  an  example,  thyroid  deficiency  produces 
a  harsh,  dry  skin,  hypopituitarism  a  smooth  one. 
Again,  the  condition  of  the  hair  would  lend  assistance, 
as  it  is  scanty  and  "  lifeless  "  in  submyxcedema,  but, 
so  far  as  the  head  is  concerned,  is  usually  the  reverse 
in  deficiency  of  the  pituitary  secretion. 

Again,  where  thyroid  deficiency  is  associated  with 
hypopiesis  and  loss  of  flesh,  with  languor  and  undue 
fatigue,  adrenal  extract  may  wisely  be  combined  with 
thyroid.  Such  treatment  will  frequently  afford  relief 
in  this  type  of  patient,  who  is  very  commonly  en- 
countered in  practice. 


308   THE  ORGANS  OF  INTERNAL  SECRETION 

There  are  on  the  market  many  pluriglandular  prep- 
arations, and  to  these  we  have  already  referred.  It 
is  scarcely  necessary  to  say  that  they  should  only  be 
given  where  the  prescriber  knows  the  exact  dose  in 
each  tablet  or  solution;  for,  if  he  is  in  ignorance  of 
the  composition  and  proportion  of  the  constituents, 
he  may  well  be  unable  to  account  for  any  untoward 
symptoms  which  arise.  It  is  probable  that  the  im- 
provement which  follows  the  employment  of  a  pluri- 
glandular preparation  is  sometimes  due  to  the  stimu- 
lating effect  it  has  upon  the  endocrine  glands  as  a 
whole.  Thus,  cases  of  acromegaly  have  been  reported 
as  cured,  or  much  relieved,  by  preparations  contain- 
ing the  extracts  of  the  thyroid,  sexual  glands,  spinal 
cord,  etc.,  presumably  by  the  restoration  of  the  hor- 
monic  balance  produced  by  the  antagonistic  extracts. 

And  now  a  few  words  to  summarize  the  utility  of 
the  more  important  organic  extracts.  We  will  turn 
our  attention  first  to  the  thymus  gland. 

Extracts  of  this  gland  have  been  used  in  a  variety 
of  diseases,  ranging  from  exophthalmic  goitre  to  de- 
ficient development.  Some  observers  speak  well  of 
its  employment  in  simple  as  well  as  exophthalmic 
goitre,  in  chlorosis,  in  rickets,  in  delayed  union  of 
fractures,  in  rheumatoid  arthritis,  and  in  deficient 
growth.  One  fact  stands  out  pre-eminently  from  the 
mass  of  supposition  in  relation  to  this  gland  and  its 
functions,  and  that  is  that  it  undoubtedly  plays  an 
important  part  in  the  calcium  metabolism  of  the  body. 

It  is  generally  admitted  that  this  gland  atrophies 


APPLICATION  OF  HORMONES  309 

about  puberty,  except  in  exceptional  cases — in  fact, 
there  appears  to  be  an  antagonism  existing  between 
the  thymus  and  the  sexual  organs.*  Ovariotomy  is 
followed  by  thymus  hypertrophy,  and  the  removal  of 
the  thymus  in  some  animals  produces  rapid  develop- 
ment of  the  sexual  organs. -j- 

Several  authorities  also  report  the  changes  in  the 
skeleton  which  have  followed  experimental  thymec- 
tomy, and  these  consist  in  deprivation  of  the  calcium 
of  the  bones,  resulting  in  spontaneous  fractures,  osteo- 
malacia, and  other  abnormalities. 

It  would  seem,  therefore,  that  the  thymus  is  con- 
cerned with  the  regulation  of  the  lime-salts  in  the  body, 
and  it  is  mainly  upon  this  assumption  that  its  extract 
has  been  administered  to  patients  suffering  from  exoph- 
thalmic goitre.  In  this  disease  the  calcium  metabo- 
lism is  defective,  and  many  authorities  maintain  that 
the  administration  of  calcium  salts  should  form  part 
of  the  treatment  in  every  instance.  Likewise,  the 
prescribing  of  extract  of  thymus  might  help  in  this 
direction,  for  it  evidently  exerts  a  favourable  influence 
in  rickets,  where  the  lime-salts  are  deficient  in  quantity. 
It  is  usually  prescribed  in  doses  ranging  from  a  few 
grains  to  half  a  drachm  daily. 

We  have  already  discussed  the  uses  of  parathyroid 
extract,   but  perhaps   we  may  here  recapitulate  the 

*  In  the  cretin,  described  by  Dr.  Middleton,  it  will  be  noted 
that  the  testes  descended  while  the  patient  was  undergoing 
thymus  administration. 

f  See  article  by  Noel  Paton,  "  The  Relation  of  the  Thymus 
to  the  Sexual  Organs,"  Journ.  Physiol.,  1905,  xxxii.  28. 


310    THE  ORGANS  OF  INTERNAL  SECRETION 

subject.  It  has  been  assumed  that  these  small  glands 
regulate  in  part  the  supply  of  calcium  to  the  cells  of 
the  body,  and  that  it  is  the  withdrawal  of  the  calcium 
which  produces  the  tetany  following  experimental 
parathyroidectomy.  On  this  assumption,  the  extract 
has  been  prescribed  in  a  variety  of  diseases,  notably 
Graves'  disease,  paralysis  agitans,  and  epilepsy.  The 
dose  is  small — a  fraction  of  a  grain  of  the  dry  extract — 
and  should  be  given  once  or  twice  daily.  We  have 
already  referred*  to  a  most  interesting  case,  reported 
by  Hurst,  in  which  definite  parathyroid  insufficiency 
was  cured  by  the  administration  of  parathyroid  extract. 

In  conclusion,  let  us  briefly  enumerate  the  organic 
extracts  which  are  at  the  disposal  of  the  practitioner, 
and  their  approximate  doses.  It  must  be  understood 
that  the  doses  are  only  approximate,  and  that  no 
attempt  is  made  to  give  an  exhaustive  list,  only  the 
more  important  of  the  extracts  being  mentioned. 

Thyroid. — The  preparations  are  the  dry  and  the 
liquid  extracts,  the  dose  of  the  former  being  from  J  to 
1  grain  for  an  initial  dose;  of  the  latter  2  or  3  minims. 
Many  products  are  upon  the  market  in  the  form  of 
elixirs,  capsules,  and  tablets,  either  alone  or  in  com- 
bination with  other  organic  extracts. 

Pituitary. — Two  classes  of  pituitary  preparations 
are  in  use,  one  manufactured  from  a  part  of  the  hypo- 
physis (usually  the  pars  posterior),  the  other  from  the 
entire  gland.  The  preparations  of  the  posterior  part  of 
the  gland  are  more  commonly  prescribed,  and  the  dose 

*  Chapter  II,  p.  47. 


APPLICATION  OF  HORMONES  311 

ranges  from  1  to  5  grains  of  the  entire  extract.  The 
dose  of  the  liquid  hypophyseal  extracts  ranges  from 
8  to  15  minims,  which  may  be  repeated  at  frequent 
intervals.  A  preparation  named  Pitglandin,  manu- 
factured from  the  anterior  lobe  of  the  pituitary  gland, 
is  supplied  by  the  British  Organo- therapy  Company. 

Adrenals. — As  we  have  already  said,  the  extract  of 
these  glands  is  more  toxic  than  that  of  the  pituitary. 
The  liquid  preparation  may  be  prescribed  in  the  form 
of  adrenalin,  the  dose  being  from  5  minims  to  \  drachm 
of  1  in  1,000  solution.  This  preparation  may  be  ad- 
ministered hypodermically.  The  dry  extract  may  be 
given  in  doses  of  1  to  3  grains. 

Pancreas. — The  average  dose  of  preparations  of  the 
pancreas  is  3  grains.  The  preparation  "  trypsogen," 
referred  to  in  the  text,  is  put  up  in  5-grain  tablets. 

Testicles. — Orchitic  extract  is  given  in  doses  rang- 
ing from  2  to  4  grains,  according  to  the  individual 
preparation.  There  are  also  many  liquid  preparations 
on  the  market,  likewise  products  combining  this  ex- 
tract with  that  of  the  central  nervous  system.  (See 
Pluriglandular  Extracts.) 

Ovary. — Extracts  of  the  corpus  luteum  are  usually 
administered.     The  average  dose  is  3  grains. 

Mammae. — The  mammary  gland  preparations  have 
been  mainly  used  for  monorrhagia,  as  an  antagonist 
to  the  ovarian  secretion  (see  note  on  pluriglandular 
preparations),  and  in  the  treatment  of  uterine  fibroids. 
The  dose  for  the  first  of  these  purposes  shoidd  begin 
at  5  grains  and  be  increased  to  about  10  grains;  to 


812  THE  ORGANS  OE  INTERNAL  SECRETION 

antagonize  hypo-oophorisni,  the  dose  must  necessarily 
be  elastic;  while  for  the  treatment  of  uterine  fibroids 
the  dose  is  about  the  same  as  that  for  menorrhagia, 
but  varies  according  to  different  authorities. 

Prostate. — The  preparations  of  the  prostate  gland 
are  given  in  doses  ranging  from  J  to  3  grains. 

Thymus. — The  dose  varies  from  3  to  10  grains.  It 
is  stated  that  care  should  be  exercised  in  prescribing 
this  extract  to  gouty  patients,  on  account  of  its  rich- 
ness in  nucleins. 

Intestine. — Preparations  of  the  duodenum  contain- 
ing pro-secretin  are  given  in  doses  of  1  to  3  grains. 
"  Secretogen  "  tablets  contain  duodenal  pro-secretin 
and  succus  entericus. 

Liver. — The  dose  varies  enormously  with  different 
preparations.  Large  doses  may  be  given,  however, 
even  up  to  1  drachm,  of  the  vacuum- dried  extract. 
An  average  dose,  however,  is  15  grains  three  or  four 
times  a  day. 

The  dose  of  bile  is  from  3  to  5  grains;  10  grains  is  a 
purgative  dose. 

Spleen. — Of  the  solid  extract,  5  grains  is  an  average 
dose;  up  to  15  minims  of  the  liquid  preparations. 

Parathyroid.  —  In  exophthalmic  goitre,  paralysis 
agitans,  chorea,  and  epilepsy,  the  dose  is  from  -^  to  ^ 
grain. 

Pluriglandular  Preparations.  —  These,  of  course, 
present  many  different  combinations.  Perhaps  the 
most  usual  combination  is  that  of  the  extracts  of 
nervous    tissue — the    brain    and    spinal    cord — with 


APPLICATION  OF  HOKMONES  313 

extracts  of  the  gonads.  To  such  a  preparation  some 
manufacturers  add  extracts  of  the  thyroid,  pituitary, 
or  thymus.  In  the  author's  opinion,  this  is  to  be 
deprecated,  as  the  reaction  of  the  patient  is  difficult 
to  judge  in  the  presence  of  such  complicating  com- 
pounds. The  correlation  of  extracts  of  the  ovary  and 
breasts  is  likewise  unwise,  as  their  actions  are  by  no 
means  similar;  in  fact,  in  some  cases — e.g.,  the  use  of 
mammary  extract  in  menorrhagia — their  effects  are 
opposed.  On  the  other  hand,  there  is  much  to  be  said 
in  favour  of  pluriglandular  therapy,  as  many  "  neuras- 
thenic "  conditions  are  undoubtedly  examples  of 
hypo-endocrinism,  and  as  such  benefit  from  this  form 
of  therapy. 

Care  is  needed,  however,  in  commencing  "  tonic  " 
treatment  by  these  means,  as  a  condition  of  irrita- 
bility— the  reaction  from  the  torpor  of  hypo-endo- 
crinism— is  apt  to  result  in  a  certain  proportion  of 
cases  when  these  preparations  are  first  administered. 
Nevertheless,  the  help  they  can  give  is  very  great, 
especially  in  functional  neuroses ;  but  the  preparation 
must  be  chosen  with  care,  and  the  reaction  of  the 
patient  to  this  form  of  medication  noted,  so  that  any 
changes  may  not  escape  notice,  as  it  may  be  necessary 
to  alter  the  component  parts  of  the  product,  and  re- 
arrange, so  to  speak,  the  proportions  of  its  constituents. 

The  present  writer  is  in  the  habit  of  picking  out  the 
extracts  which  he  considers  are  required  in  an  indi- 
vidual case,  and  combining  them  in  the  proportions 
which   seem   most   suitable.      In   this    way   a    more 


314    THE  OEGANS  OF  INTERNAL  SECRETION 

accurate  dosage  is  possible,  and  the  constituents  may 
be  readjusted  should  this  be  necessary. 

This,  then,  is  a  brief  summary  of  the  more  impor- 
tant organic  extracts  which  are  available  for  adminis- 
tration, although  the  list  is  by  no  means  exhaustive. 

Every  medical  man  encounters  from  time  to  time 
cases  which  are  not  relieved  or  even  benefited  by 
ordinary  methods  of  treatment.  In  many  of  these 
patients  relief  would  be  afforded,  if  not  actual  cure, 
by  organo-therapy. 

In  the  following  chapter  some  practical  points  in 
hormone- therapy  are  dealt  with.  It  is  hoped  that  this 
chapter  will  be  of  help  to  those  unfamiliar  with  the 
practice  of  organo-therapy. 

Reference. 
1  Harrower,  Practical  Hormone-Therapy,  pp.  22,  23. 


CHAPTER  XIV 
PRACTICAL  POINTS  IN  HORMONE-THERAPY 

There  are  many  disorders  where  endocrine  disturb- 
ance may  be  expected,  but  where  the  signs  indicative 
of  gross  disorganization  are  lacking. 

In  some  instances  there  are  symptoms  suggestive  of 
a  state  61  hypothyroidism,  but  there  are  also  present 
features  which  contradict  such  a  diagnosis,  and  even 
contra-indicate  the  administration  of  thyroid  extract. 
Those  cases  in  which  help  can  be  derived  from  the 
history  are,  of  course,  easier  so  far  as  the  commence- 
ment of  treatment  by  organo-therapy  is  concerned. 

So  far  as  the  practical  experience  of  the  present 
writer  is  concerned,  the  utilization  of  organic  extracts 
requires  nice  judgment  if  we  are  to  obtain  satisfactory 
results.  The  data  are  often  so  few  or  so  slight  in 
character,  and  our  exact  knowledge  of  the  small  signs 
of  pluriglandular  disturbance  is  so  deficient,  that  at 
this  stage  in  the  progress  of  this  method  of  treatment 
the  physician  must  rely  upon  his  practical  handling 
of  the  individual  case,  to  compensate  for  the  lack  of 
exactness  in  diagnosis.  Nevertheless,  if  we  judiciously 
weigh  the  evidence  in  any  given  case,  and  if  we  are 
possessed  of  such  knowledge  as  experimental  physi- 

315 


316    THE  OKGANS  OF  INTERNAL  SECRETION 

ology  and  clinical  practice  can  give  us,  we  shall  very 
often  find  that  we  can  help  patients  who  are  not 
making  progress  under  other  methods  of  treatment. 
We  should  learn  to  judge  how  long  a  particular  extract 
should  be  persevered  with;  what  signs  of  its  action  to 
look  for;  and  when  we  should  alter  its  dose  or  change 
the  prescription.  In  this  relation,  organo-therapy  is 
analogous  to  the  utilization  of  the  inorganic  drugs  in 
the  pharmacopoeia;  it  is  necessary  to  know,  not  only 
the  physiological  effects  of  our  minerals,  but  also  any 
toxicological  results  which  might  accrue  were  the  dose 
unsuitable. 

The  diagnosis  of  disorders,  in  which  the  secretion  of 
one  gland  is  patently  deficient,  is  relatively  a  simple 
matter,  although  treatment  does  not  necessarily  end 
when  one  has  ordered  an  extract  of  the  gland  in  a 
suitable  dose.  Better  results  may  often  be  obtained 
by  giving  a  pluriglandular  preparation,  for  in  some 
cases  the  outstanding  deficiency  has  led  to  secondary 
complications.  Such  a  syndrome  is  better  dealt  with 
by  a  combination  of  extracts.  But  the  larger  propor- 
tion of  patients  present  no  such  helpful  guide  as  a 
single  glaring  defect.  If  this  were  the  case  we  should 
be  able  to  diagnose  our  patients  in  the  streets,  as,  for 
example,  it  is  possible  to  do  with  acromegalics  and  sub- 
thyroidics.  There  are,  speaking  in  general  terms,  two 
systems  which  will  bear  a  close  scrutiny  whenever  we 
prescribe  an  organic  extract;  and  these  systems  are 
intimately  related  to  each  other.  They  are  the  cardio- 
vascular, and  the  excretory;  and  from  the  study  of 


PEACTICAL  POINTS  317 

how  these  two  units  are  behaving  much  information 
can  be  obtained.  It  is  not  necessary  to  point  out,  and 
still  more  unnecessary  to  apologize  for,  the  fact  that 
many  of  the  statements  in  this  chapter  are  elaborated 
upon  what  may  be  regarded  as  slender  foundations. 
In  a  science  as  youthful  as  this,  we  must  utilize  what 
lies  to  our  hands,  discarding  what  is  worthless  as  some- 
thing better  is  found. 

In  approaching  a  particular  case  we  have  first  to 
decide  whether  there  is  an  endocrine  disturbance; 
next,  which  part  of  the  hormone-balance  is  upset; 
then,  whether  it  is  a  disturbance  in  which  organo- 
therapy would  be  useful;  and,  finally,  which  product 
or  combination  of  products  would  be  suitable. 

To  take  an  example  in  order  to  make  our  meaning 
clear.  Juvenile  obesity  is  a  condition  by  no  means 
rare.  With  it  are  associated,  in  a  certain  proportion 
of  cases,  physical  mal- development  and  mental 
backwardness.  There  are  frequently  no  very  tangible 
physical  signs  apart  from  the  general  clinical  picture. 
Now  take  two  children,  both  belonging  to  this  group; 
one  will  do  well  on  thyroid,  the  other  will  make  no 
progress,  however  carefully  and  skilfully  the  extract 
is  handled.  The  extract  here  may  have  been  given, 
either  because  a  diagnosis  of  hypothyroidism  has  been 
arrived  at,  or  because  of  its  physiological  effects. 

To  continue  with  our  example.  What  treatment  is 
to  be  adopted  in  the  case  of  the  second  child  ?  We 
know  that  hypopituitarism  presents  features  similar  to 
those  of  hypothyroidism.     Pituitary  extract  may  serve 


318  THE  OEGANS  OF  INTEKNAL  SECKETION 

to  regulate  the  disordered  metabolism.  If  so,  the  child 
will  improve  mentally  as  well  as  physically;  but  some- 
times in  these  cases — and  most  practitioners  can  recall 
cases  of  this  kind — both  thyroid  and  pituitary  fail. 
Here  we  arrive  at  the  utility  of  an  extract  from  its 
third  aspect — namely,  empiricism.  Physiology  teaches 
us  that  the  thymus  and  the  gonads  are,  so  far  as  growth 
is  concerned,  antagonistic,  and  that  the  former  wanes 
as  the  latter  waxes.  If  the  child  is  small  of  stature, 
extract  of  thymus  might  help,  inasmuch  as  it  improves 
the  general  nutrition  and  stimulates  growth.  Or, 
again,  if  the  symptoms  are  associated  with  delayed 
puberty,  extract  of  the  ovary  or  corpus  luteum  might 
help  in  the  regulation  of  metabolism  and  the  promotion 
of  adequate  oxidation  of  the  tissues.  Again,  we  might 
summon  help  from  the  chromaffin  tissue,  assume  that 
some  passing  infection  has  produced  a  hypo-adrenia, 
and  prescribe  adrenal  extract.  Finally,  we  might 
order  a  compound — the  pluriglandular  product. 

I  have  purposely  put  the  case  in  this  way  and  its 
treatment,  because  it  is  a  good  example  of  the  problems 
which  face  the  organo-therapist  and  the  possibilities  of 
treatment  between  which  he  has  to  decide. 

He  will  remember  that  in  many  cases  of  submyx- 
cedema  the  anterior  lobe  of  the  pituitary  has  been  found 
to  be  enlarged;  and  we  have  already  pointed  out  that 
this  may  be  an  attempt  to  prevent  the  stagnation  con- 
sequent upon  deficiency  of  thyroid.  If,  however, 
pituitary  extract  fails  to  help  the  condition,  we  must 
assume  that  another  hormone  is  required  and  must 


PKACTICAL  POINTS  319 

endeavour  to  supply  it.  It  is  wise  to  bear  in  mind 
that  there  is  a  definite  complementary  action  among 
the  internal  secretions,  and  that  deficiency  of  one 
hormone  can  be  compensated  for  by  the  vicarious 
overtime  of  another. 

There  is  no  need  to  labour  this  point.  It  will  be 
obvious  that  many  of  the  indications  upon  which  we 
prescribe  organic  extracts  are  of  the  flimsiest  structure. 
This  must  needs  be  so  in  any  new  method,  and  time 
and  experience  alone  will  enable  us  to  "hit  the  bull's- 
eye  "  the  first  time;  indeed,  we  are  sometimes  fortunate 
if  we  hit  the  target  at  all,  when  we  consider  the  dis- 
advantages under  which  we  labour. 

The  Utility  of  Empirical  Prescribing. 

There  are  certain  extracts  to  be  found  in  the  cata- 
logues of  most  manufacturers,  the  utility  of  which  is 
not  supported  by  physiological  evidence,  at  any  rate 
not  conclusively  so.  Of  these,  splenic  extract  is  an 
example.  It  is  recommended  for  use  in  anaemia  and 
chlorosis,  and  for  raising  the  resistance  to  infection, 
notably  in  tuberculosis.  It  is  stated  that  it  stimulates 
nutrition  and  augments  the  body- weight,  increasing  at 
the  same  time  the  leucocyte  count.  How  does  the 
evidence  of  physiologists  support  this  ?  Kecent  ex- 
periments on  the  internal  secretions,  reported  in 
Sajous's  work,  show  that  the  spleen  is  concerned  in 
digestion;  the  experiments  which  are  particularly  con- 
vincing in   this   connection   are   those  of  Scruff  and 


320   THE  OEGANS  OF  INTERNAL  SECRETION 

Herzen.  These  observers  showed  that  pancreatic 
digestion  was  impaired  or  stopped  when  the  splenic 
vessels  had  been  ligatured.  Sajous  says:  "It  is 
evident  that.,  if — as  believed  by  Schiff  and  Herzen — 
the  circulatory  cycle  must  be  traversed  by  the  splenic 
ferment  before  the  pancreas  can  be  influenced  by  it, 
this  ferment  will  merely  pass  through  the  pancreas 
without  in  any  way  converting  trypsinogen  into 
trypsin,  and  fruitlessly  re-enter  the  splenic  venous 
current."*  This  author  continues  to  develop  the 
theory  that  the  spleen  is  concerned  in  the  processes  of 
digestion,  in  which  function  it  stands  intimately  related 
to  the  pancreas.  Without  further  describing  the 
evidence — which  is  long  and  technical — we  may  say 
that  such  evidence  as  has  been  produced  by  recent 
laboratory  work  is  on  the  side  of  the  argument  that 
the  spleen  possesses  an  internal  secretion  which  is 
concerned  in  digestion. 

Now  for  the  practical  question.  To  what  utility 
can  extracts  of  the  spleen  be  put?  On  p.  227  we 
refer  to  the  hormone  which  has  a  stimulating  effect 
upon  peristalsis.  This  substance  is  stored  in  the 
spleen,  and  is  in  use  for  the  treatment  of  chronic  con- 
stipation. After  injection  into  an  animal  the  increase 
in  peristalsis  can  be  seen  to  be  very  marked.  In  one 
patient  whom  the  present  writer  had  under  his  care 
hypodermic  injections  of  splenic  extract  were  ordered 
to  endeavour  to  raise  his  resistance,  as  there  was  an 
infection,  the    nature    of  which  was    not    diagnosed, 

*  P.  393. 


PEACTICAL  POINTS  321 

which  was  progressive  and  causing  anaemia,  I033  of 
weight,  and  general  bodily  weakness.  The  effect  of 
this  treatment  was  steadily  to  raise  the  body- weight 
and  strength,  and  to  abolish  the  nocturnal  temperature 
and  sweats.  But  perhaps  the  most  interesting  result 
achieved  was  that  the  constipation  and  indigestion, 
which  was  of  long  standing,  improved  markedly  as  the 
treatment  went  on,  and  after  some  months  the  patient 
required  practically  no  aperients,  had  lost  his  i:  yellow  " 
colour  (the  latter  a  sure  sign  of  toxaemia),  and  no 
longer  suffered  from  indigestion. 

This  case  was  an  example  of  the  utilization  of  an 
extract,  without  very  much  physiological  support. 
For,  although  the  spleen  is  known  to  be  concerned  in 
the  replacement  of  the  white  cells  and  the  destruction 
of  used-up  cells,  the  evidence  that  its  extracts  are 
therapeutically  valuable  is  of  the  slightest.  From 
the  histological  standpoint  it  cannot  be  called  a  ductless 
gland  because  it  is  not  composed  of  epithelial  cells; 
nevertheless,  as  we  have  already  said,  evidence  is  being 
collected  to  show  that  it  is  concerned  in  the  formation 
of  internal  secretory  substances. 

Administration  of  splenic  extract  has  been  attended 

with  success  in  several  disorders.     In  the  case  quoted 

above,  the  main  factor,  in  the  present  writer's  opinion, 

was  the  presence  of  a  toxaemia,  and  this  was  in  all 

probability  of  an  intestinal  origin.     It  is  suggested, 

therefore,  that  the  injections  of  splenic  extract  helped 

to  neutralize  these,  and  to  raise  the  haemic  resistances, 

This  is,  of  course,  speculation;  but  if  such  treatment- 

21 


822    THE  ORGANS  OF  INTERNAL  SECRETION 

after  a  more  extended  trial,  can  be  shown  to  be  effica- 
cious, we  may  perhaps  be  able  to  add  to  our  thera- 
peutic weapons  in  the  treatment  of  alimentary  toxaemia. 

The  use  of  splenic  extract  in  the  treatment  of  tuber- 
culosis is  well  known.  Boyle,  of  Cannes,  speaks  in  the 
highest  terms  of  the  success  which  has  attended  its 
employment  in  the  treatment  of  this  disorder,  and  his 
results  certainly  bear  out  his  contentions.  Other 
observers  have  reported  success  following  upon  this 
method  of  treatment. 

Extracts  of  spleen  have  been  utilized  in  diseases  of 
the  spleen,  and  in  patients  where  the  spleen  is  enlarged. 
It  has  also  been  employed  in  cases  of  typhoid,  malaria, 
and  in  blood  diseases.  In  the  latter  its  influence  is 
mainly  upon  the  leucocyte  count;  and  that  this  result 
is  not  obtained  by  the  nuclein  content  of  the  extract 
is  shown  by  the  fact  that  other  extracts — namely, 
thyroid,  liver,  and  kidney  —  had  no  such  effect.* 
In  many  cases  of  toxaemia,  extract  of  spleen  will  be 
helpful,  and  this  is,  perhaps,  particularly  true  in 
intestinal  toxaemia.  In  the  patient  referred  to  above, 
injections  of  splenic  extract  (British  Organo-therapy 
Co.)  were  employed  and  were  divided  into  several 
courses  of  a  dozen,  three  being  given  a  week,  with  an 
interval  of  a  fortnight  at  the  end  of  each  course.  No 
undue  reaction — either  local  or  general — was  noticed 
at  any  time;  but  on  one  occasion  when  the  injections 
were  omitted  for  rather  longer  than  usual  (during  the 

*  Quoted  in  "  Practical  Hormone-Therapv,"  by  H.  Harrower, 
p.  132. 


PEACTICAL  POINTS  323 

earlier  part  of  the  treatment),  the  patient  began  to 
lose  weight. 

We  have  already  referred  to  the  utility  of  adrenal 
extract.  It  may  be  helpful  here  to  indicate  in  a  little 
more  detail  practical  points  in  its  administration. 

The  present  writer  is  in  the  habit  of  commencing 
with  small  doses  of  the  extract  by  mouth  (e.g.,  2-gr. 
capsule,  British  Organo-therapy  Co.,  or  \  drachm  of 
the  Elixir,  Allen  and  Hanbury),  and  gradually  in- 
creasing this  dose  until  the  maximum  recommended  by 
the  manufacturer  of  the  particular  preparation  is 
reached.  If  no  undue  reaction  is  recorded,  and  if  the 
patient  has  shown  no  signs  of  improvement,  injections 
can  be  given  twice  or  thrice  a  week  in  the  buttock. 
In  the  "  exhaustion  "  cases  already  mentioned,  signs 
of  hypo-adrenia  are  often  found,  and  in  some  instances 
the  presence  of  indicanuria  points  to  the  concurrent 
existence  of  intestinal  mal- assimilation  or  stasis.  It 
may  be  that  this  latter  condition  is  the  cause  of  the 
adrenal  exhaustion,  but,  in  any  case,  such  patients 
frequently  derive  much  help  from  adrenal  therapy. 

In  some  instances  (and  this  has  been  recommended 
by  other  writers  on  this  subject)  the  combination  of 
adrenal  and  pituitary  extracts  is  more  successful  than 
either  singly.  It  is  often  a  good  plan  to  administer 
pituitary  extract  (whole  gland)  by  the  mouth  twice 
or  thrice  daily,  and  adrenal  extract  intramuscularly 
twice  or  thrice  a  week.  In  obese  patients  (it  has  been 
said  that  the  obese  neurasthenic  is  the  most  troublesome 
to  treat)  extract  of  the  anterior  lobe  of  the  pituitary 


324    THE  ORGANS  OF  INTERNAL  SECRETION 

gland  is  preferable,  as  its  effect  upon  metabolism  is 
more  speedily  noticed.  Small  doses  of  thyroid  gland 
— i  to  J  grain  at  bed-time — assist  excretion  without 
interfering  with  the  routine  treatment. 

It  may  be  mentioned  here  that  the  contra-indications 
to  the  administration  of  adrenal  gland  must  be  borne 
in  mind  in  every  case  before  even  oral  doses  are  given. 
Arterio-sclerosis,  or  persistent  hyperpiesis,*  diabetes,  or 
glycosuria,  phthisis,  haemoptysis,  and  many  cases 
where  digestive  disturbances  are  in  evidence,  are  un- 
suitable for  adrenal  therapy.  It  is  also  somewhat 
risky  to  prescribe  this  extract  where  the  nervous  system 
is  unstable,  where  the  patient  is  emotional  and  ex- 
citable, although  adrenal  therapy  is  often  recom- 
mended to  overcome  the  physical  state  ensuing  after 
psychical  strain. 

Backward  children  can  often  be  helped  by  organo- 
therapy. In  Chapter  VI.  we  refer  to  two  cases  of  this 
kind  reported  by  Magnier,  which  had  benefited 
markedly  by  the  administration  of  anterior  lobe  of  the 
pituitary.  If  this  fails,  or  if  it  appears  to  be  contra- 
indicated,  other  extracts  are  available.  Let  me  draw 
attention  to  a  type  of  child  frequently  encountered  in 
the  consulting-room.  The  mother  brings  the  child 
complaining  that  he  or  she  is  dull,  "  cannot  understand 
like  other  children,"  is  not  making  progress  at  school, 
and,  perhaps,  will  not  play  or  mix  with  other  children 

*  We  have  pointed  out  that  several  sphygmanometric  readings 
are  necessary  in  these  cases,  as  the  blood-pressure  varies  markedly 
from  time  to  time. 


PRACTICAL  POINTS  325 

of  his  own  age.  On  examination,  the  child  has  what 
Magnier  calls  a  "  sheepish  look,"  is  obviously  of 
sluggish  mentality,  answers  questions  slowly  and  is 
generally  stolid,  mentally  and  physically.  There  is 
sometimes  a  history  of  bed-wetting,  or  it  is  even  a 
symptom  up  to  date.  The  hmbs  are  often  clumsy, 
and  I  have  frequently  been  struck  by  the  large  size  of 
the  bones,  more  particularly  those  forming  the  knee- 
joint.  The  skin  of  such  children  is  smooth  and 
singularly  hairless,  and  the  child  or  mother  will  admit 
on  questioning  that  he  does  not  sweat  like  ordinary 
children. 

This  type  of  case  I  regard  as  being  due  to  hypo- 
pituitarism, for  two  reasons.  First,  because  the 
symptoms  point  in  that  direction,  although  these 
obviously  vary  according  to  the  stage  at  which  one 
sees  the  patient;  second,  because  of  the  improvement 
which  follows  the  exhibition  of  pituitary  extract.  It 
may  be  that  the  patient  is  suffering  from  dyspitui- 
tarism;*  and  that  symptoms  of  past  hyperpituitarism 
are  mingled  with  present  hypopituitarism.  This,  it 
seems  to  me,  accounts  for  the  heterogeneous  and  con- 
tradictory features  of  many  of  these  cases,  seen  from 
the  point  of  view  of  the  organo-therapist;  and  it  makes 
the  choice  of  an  initial  treatment  a  difficult  matter. 

There  is,  however,  one  feature  of  these  patients  which 
is  definite,  and  which  indicates  plainly  a  line  of  treat- 

*  See  p.  138  for  a  reference  to  this  condition.  Also  compare 
the  cases  just  described  with  Frohlich's  sjudrome,  or  dystrophia 
adiposo-genitalis. 


326    THE  OBGANS  OF  INTEENAL  SECEETION 

merit,  and  that  is  inertia  shown  mentally  by  the  slow- 
ness of  comprehension,  and  physically  by  the  sluggish- 
ness of  the  circulation,  the  deficient  elimination,  and 
the  retention  of  metabolic  products  in  the  form  of  fat. 

Thyroid,  pituitary,  and  extracts  of  the  gonads  all 
improve  this  condition,  and  the  decision  as  to  which 
shall  be  utilized  in  an  individual  case  depends  upon  the 
correlation  of  other  symptoms.  The  calcium  metabo- 
lism of  the  body  is  profoundly  disturbed  in  these 
patients;  in  fact,  they  present  the  opposite  picture 
clinically  to  the  bright- eyed,  eager,  and  restless  hyper- 
thyroidic.  Bradley  Figgis  describes  the  backward 
child  we  are  discussing:  "  At  school,  the  dull,  slow- 
witted,  apathetic  boy,  with  heavy  bones  and  a  tendency 
to  grossness  of  body,  as  well  as  his  eager,  restless, 
impulsive  brother,  with  no  great  power  of  concentration 
or  perseverance,  are  both  amenable  to  the  action  of 
these  secretions  affecting  calcium  and  general  metabo- 
lism. It  may  yet  be  possible  to  add  a  cubit  to  one's 
stature  by  a  course  of  pituitarin  or  other  extract.  At 
puberty,  and  during  sexual  life,  abnormalities  of 
growth  and  functioning  and  morbid  tendencies  may 
be  corrected  by  pituitary,  thyroid,  mammary,  or 
ovarian  extracts."* 

So  large  a  part  does  the  pituitary  play  during 
development  that  one  is  almost  inclined  to  commence 
the  organo-therapeutic  treatment  of  these  cases  with 
extract  of  this  gland,  assisted  by  small  doses  of  thyroid 

*  "  The  Empire  of  the  Ductless  Glands,"  The  Medical  Press, 
September  20,  1920,  p.  249. 


PEACTICAL  POINTS  327 

extract.  But  the  thymus  has  given  good  results  in 
some  cases;  while  pluriglandular  preparations  can 
justly  claim  our  attention  if  only  on  account  of  the 
wider  field  they  occupy. 

I  have  treated  cases  of  this  nature  with  pitglandin,  a 
preparation  of  the  anterior  lobe  of  the  pituitary,  with 
good  results.  I  have  also  employed  the  same  prepara- 
tion in  obesity  in  adults. 

A  condition  analogous  to  this,  but  occurring  in 
adolescence,  and  often  difficult  to  ameliorate  by 
ordinary  measures,  can  frequently  be  improved  by 
organo-therapy.  In  one  patient  under  my  care,  a  boy 
of  sixteen,  there  is  absence  of  one  testicle  (removed 
during  an  operation),  while  the  other  has  been  stitched 
inside  the  peritoneal  cavity.  This  patient  has  been 
taking  a  pluriglandular  preparation  for  a  very  long 
time,  as,  if  he  omits  this  treatment,  he  begins  to  develope 
a  sluggish  mentality,  to  be  unable  to  do  his  school  work, 
and  to  suffer  from  obesity,  chilblains,  etc. 

The  fact  that  better  results  are  obtained  by  a  mixed 
preparation  than  by  orchitic  extract  alone  suggests 
that  the  absence  of  the  secretion  of  the  interstitial 
gland  has  upset  other  of  the  internal  secretions. 

The  case  reported  in  the  last  chapter,  where  the  boy 
of  seven  years,  suffering  from  double  undescended 
testis,  was  treated  by  thymus  gland  and  hormotone  in 
combination,  with  the  result  that  the  testes  had 
descended  after  five  weeks,  suggests  that  extracts  other 
than  those  of  the  gonads  are  worthy  of  employment  in 
these  cases. 


328  THE  ORGANS  OF  INTERNAL  SECRETION 

Perhaps  no  field  exists  offering  such  a  wide  opening 
to  the  organo-therapist  as  that  of  the  backward  child; 
and  any  physician  who  has  treated  patients  by  these 
methods  will  agree  that  during  development  full  use 
can  and  should  be  made  of  the  help  to  be  derived  from 
organo-therapy. 

During  adolescence  and  the  third  and  fourth  decades 
of  life,  cases  are  encountered  in  many  ways  analogous 
to  the  backward  child  just  described.  These  are 
frequently  instances  of  hypothyroidism,  but  they  are 
mentioned  here  in  order  that  points  in  their  treatment 
may  be  referred  to.  The  patient — often  a  woman — 
complains  of  physical  and  mental  languor,  associated 
with  increase  in  the  body- weight;  or  some  "  rheumatic  " 
affection  such  as  stiff  joints,  lumbago,  or  "  muscular 
rheumatism,"  is  a  common  concurrence.  The  elimina- 
tion in  these  patients  is  often  faulty;  they  complain  of 
constipation  and  digestive  disturbances,  the  urine  is 
concentrated  and  contains  phosphates,  urates,  and 
sometimes  indican;  while  they  will  probably  admit 
that  they  rarely,  if  ever,  sweat.  It  is  generally  a 
matter  of  difficulty  to  establish  a  definite  onset,  and 
perhaps  even  careful  questioning  will  not  succeed  in 
eliciting  a  definite  period  during  which  the  health  has 
been  bad.  On  the  other  hand,  there  may  be  details  in 
the  history  worthy  of  note  from  the  etiological  point 
of  view.  Thus,  a  patient  presenting  the  above  features 
recently  informed  the  present  writer  that  all  these 
symptoms  were  at  the  worst  during  the  catamenia,  in 
fact  were  comparatively  negligible  except  at  such  times. 


PRACTICAL  POINTS  329 

Such  a  syndrome  might  be  explained  on  the  ground 
of  reflex  disturbance  of  function,  the  blame  being 
placed  upon  the  nervous  system.  From  the  thera- 
peutic view-point  something  more  helpful  is  required, 
and  this  can  be  supplied  by  organo- therapy.  In  all 
such  cases  as  these  the  basis  of  treatment  should  be 
founded  upon  the  aim  of  increasing  elimination. 
Exactly  how  this  can  be  accomplished  will  depend 
upon  the  results  of  the  physical  examination.  Assuming 
that  such  means  as  laxatives,  diet,  and  adequate 
exercise  have  been  instituted  to  increase  elimination, 
we  must  consider  which  of  the  "  big  three  "  among  the 
endocrine  eliminants  should  be  prescribed.  Thyroid, 
pituitary,  or  the  gonads — one  or  more  of  these  will  be 
required.  If  there  are  any  indications  of  hypothyroidism 
upon  examination,  treatment  should  commence  by  small 
doses  of  thyroid  extract  given  at  bedtime.  Pituitary 
extract,  whole  gland  or  anterior  lobe,  is  of  real  value 
in  these  patients,  and  can  be  given  in  conjunction  with 
the  thyroid.  While  it  is  not  possible  to  lay  down  any 
hard-and-fast  rule  as  to  dosage,  \  grain  of  thyroid  at 
bedtime,  and  from  \\  to  2|  grains  of  pituitary  extract 
twice  daily  is  somewhere  around  what  will  be  found 
to  be  suitable  in  the  average  case. 

There  are  several  ways  in  which  thyroid  extract  can 
be  helpfully  administered  to  patients  who  require  it 
over  a  long  period.  One  method  which  has  gained 
popularity  is  to  give  the  extract  for  three  weeks  every 
month,  and  omit  it  for  one  week.  This  is  designed  to 
prevent  undue  accumulation  of  the  iodothyrin,  which 


330    THE  ORGANS  OF  INTERNAL  SECRETION 

has  sometimes  been  found  to  lead  to  symptoms  such  as 
tremors  and  jumpiness.  Another  method  is  to  forbid 
the  patient  to  take  the  extract  at  any  other  time  except 
the  last  thing  at  night,  by  which  means  rest  in  the 
recumbent  position  is  assured  after  the  dose,  and 
larger  doses  can  be  given  without  risk  of  palpitation 
or  other  unpleasant  sequelae.  This  I  have  found  to  be  a 
good  plan,  and  I  also  insist  upon  the  dose  being  reduced 
or  omitted  altogether  in  the  event  of  the  patient  being 
called  upon  to  undergo  undue  exertion  of  either  mind 
or  body. 

The  lymphatic  type  of  patient  whom  we  have 
described  improves  markedly  under  thyroid  treatment; 
the  weight  decreases,  the  functions  improve,  and  the 
feeling  of  well-being  is  again  experienced.  A  note  of 
warning  is  perhaps  needed  as  to  the  administration  of 
too  generous  doses;  not  only  is  it  dangerous,  but  it 
frequently  defeats  its  own  object,  for  such  patients 
improve  much  more  steadily,  if  we  are  content  to  take 
our  time  over  the  treatment,  than  if  we  are  impatient 
to  see  results.  Again,  if  symptoms  of  "  nervousness  " 
develope,  it  is  better  to  leave  off  the  thyroid  for  a  week 
or  two  and  insist  upon  increased  rest  until  the  con- 
dition improves ;  it  is  not  uncommon  for  such  symptoms 
to  manifest  themselves  while  thyroid-therapy  is  in 
progress. 

The  rule  in  all  organo-therapy  should  be  a  small 
initial  dose,  a  gradual  increase,  and  a  cessation  if 
symptoms  develope  while  the  treatment  is  in  progress. 


CHAPTEE  XV 
CONCLUSIONS 

Having  dealt  with  the  pathology  and  treatment  of  the 
organs  of  internal  secretion,  and  having  briefly  out- 
lined the  organic  extracts  which  may  be  utilized  in  the 
treatment  of  disease,  it  may  not  be  out  of  place  at  this 
point  to  discuss  the  present  place  of  hormone- therapy 
in  medicine. 

Not  many  years  ago  an  eminent  physician,  in  speak- 
ing of  the  use  of  medicines,  said  that  in  prescribing  a 
drug  a  medical  man  was  putting  a  substance  of  whose 
properties  he  knew  little  into  a  body  about  which  he 
knew  less.  This  may  be  only  too  true  with  reference 
to  the  administration  of  inorganic  chemicals,  or,  rather, 
with  reference  to  certain  inorganic  chemicals ;  but  now 
that  organo-therapy  has  become  an  established  method 
of  treatment,  it  can  scarcely  be  applied  indiscrimi- 
nately to  all  forms  of  prescribing.  But  it  cannot  be 
denied  that  much  drug-therapy  is  empirical,  and  is 
resorted  to  in  the  hope  of  counteracting  morbid  con- 
ditions of  the  body,  and  that  much  of  such  treatment 
would  be  quite  useless  were  it  not  accompanied  by  the 
hope  and  faith  of  the  patient. 

331 


332  THE  OEGANS  OF  INTEENAL  SECRETION 

In  prescribing  organic  extracts,  however,  we  are 
endeavouring  to  counteract  morbid  states  by  admin- 
istering the  substance  the  deficiencv  of  which  we 
believe  to  have  caused  the  condition.  We  gather  to- 
gether the  salient  features  of  an  individual  case,  and 
compare  the  syndrome  with  that  winch  is  known  to  be 
present  in  derangements  definitely  due  to  disturbances 
of  the  hormone  balance.  If  this  points  decidedly  to 
a  deficiency  of  one  hormone  the  path  is  clear,  and  the 
result  will  be  steady  improvement  to  cure.  But  if 
a  multiple  disturbance  is  present,  and  it  must  be 
remembered  that  this  is  very  often  the  case,  the 
course  of  the  treatment  will  not  be  so  smooth,  neither 
can  the  first  combination  be  expected  to  prove  suc- 
cessful. 

Nevertheless,  even  with  this  class  of  case,  the  adop- 
tion of  organo- therapy  is  less  speculative  than  is 
the  prescription  of  many  inorganic  remedies,  which, 
in  ameliorating  one  symptom,  are  prone  to  initiate 
another.  With  obvious  hypothyroidism  or  hypo- 
pituitarism, the  only  remedy  which  will  give  a  speedy 
and  satisfactory  cure  is  the  administration  of  the 
organic  extract  whose  deficiency  has  produced  the 
symptoms.  But,  apart  from  such  straightforward 
cases  as  these,  there  are  a  host  of  physical  and  mental 
deviations  from  normal  health  which  may  be  rectified 
by  this  method  of  treatment. 

We  have  already  outlined  these,  but  we  desire  to 
emphasize  in  this  chapter  that  the  use  of  organic 
preparations  is  now  an  established  method  of  treating 


CONCLUSIONS  333 

disease,  and  one  which  will  undoubtedly  form  a  large 
part  of  treatment  in  the  future. 

In  an  article  dealing  with  the  question  of  the  treat- 
ment of  disease  which  was   published  recently  in  a 
prominent  journal,  the  opinion  was  expressed  that  the 
majority  of  chronic  diseases  of  middle  age  could  only 
be  palliated — that   their  cure  was   impossible.     The 
writer  proceeded  to   emphasize  the  fact   that   these 
diseases  arise  during  early  youth,  and  that  our  ignor- 
ance of  the  origin  of  chronic  disease  is  profound.     This 
latter  statement  is,   unfortunately,   correct;   but  the 
first  clause  which  we  have  quoted  was  probably  truer 
twenty  years  ago  than  it  is  now.     For  every  year  that 
passes  increases  our  knowledge  of  the  efficacy  of  modern 
methods  of  treatment,  and  not  least  among  these  we 
must  class  organo-therapy.     Before  the  discovery  that 
myxcedema  owed  its  origin  to  atrophy  of  the  thyroid 
gland,  and  that  the  symptoms  caused  thereby  yielded 
to  the  administration  of  extracts  of  this  gland,  the 
features  of  this  malady  were  hopelessly  intangible,  and 
their  treatment,  either  as  individual  symptoms  or  a 
syndrome,  impossible.     This  disease  may  be  included 
among  those  which  the  writer  of  this  article  had  in 
mind;  but  although  the  actual  cause  of  the  atrophy  is 
unknown,  it  is  quite  untrue  to  say  that  its  palliation 
only   is    possible.     For    both   in   the   grosser   disease 
myxcedema  and  in  the  lesser  malady  submyxcedema, 
the  administration  of  thyroid  gland  is  curative — in  so 
far  as  the  disappearance  of  symptoms  constitutes  a 
cure.     It  is  quite  true  that  the  treatment  must  be  con- 


334  THE  OEGANS  OF  INTERNAL  SECRETION 

tinued,  even  throughout  life,  but  so  long  as  it  prevents 
the  disease  from  persevering,  we  have  achieved  what 
may  be  called  a  cure. 

This  is  only  one  disease,  and  one  among  thousands; 
but  it  is  nowadays  curable,  and  it  is  probable  that, 
with  the  advance  of  our  knowledge  on  these  lines, 
many  other  lesions  included  in  the  past  among  the 
incurable  or  chronic  disorders  will  yield  to  modern 
therapy.  Not  only  the  vague  neuroses — the  neuras- 
thenic, the  neurotic,  or  the  hypersensitive  patients, 
whose  existence  is  due  to  the  civilization  we  boast  of — 
but  diseases  which,  in  the  past,  have  left  their  victims 
more  or  less  crippled  for  life,  will  in  the  future  probably 
be  treated  so  that  they  no  longer  maim  permanently. 

Many  of  these  diseases  are  accountable  for  the  de- 
rangements seen  in  middle  age,  and  by  the  time 
advice  is  sought  the  machine  can  only  be  repaired,  not 
restored.  But  the  repairs  will  be  less  needed  when 
our  knowledge  of  the  treatment  of  the  diseases  inci- 
dental to  childhood  is  improved,  and  it  may  be  that 
the  endocrine  glands  will  figure  largely  in  such  im- 
provement. If,  for  example,  we  can  increase  the 
defences  of  the  body  against  infection  by  the  admin- 
istration of  an  organic  extract  (as  is  now  done  in  the 
case  of  tuberculosis),  we  shall  have  developed  a  weapon 
against  which  the  onslaught  of  micro-organisms  will  be 
weakened,  if  not  defeated.  In  which  case  the  germs 
responsible  for  the  exanthemata,  with  their  damaging 
sequelae,  will  find  their  task  less  easy  than  formerly. 

Even  the  organic  changes  which  we  are  accustomed 


CONCLUSIONS  B35 

to  regard  as  inseparable  from  middle  and  old  age  may 
be  remedied  or  averted  by  the  employment  of  organic 
extracts.     An  example  will  serve  to  make  our  meaning 
clearer.     The  complex  metabolism  of  the  body  appears 
to  be  regulated  by  the  organs  of  internal  secretion;  a 
deficiency  or  excess  of  one  of  these  important  corre- 
lators is  able  so  to  upset  the  metabolism  that  sub- 
stances, often  of  a  noxious  nature,  are  stored  in  the 
body  instead  of  being  ehminated  by  the  usual  channels. 
In  course  of  time  this  gradual  retention  may  produce 
a  metabolic  disease  such  as  gout  or  diabetes,  and  it 
may  assist  in  the  well-known  accompanying  changes 
such  as  are  present  in  chronic  interstitial  nephritis,  in 
hepatic  cirrhosis,  in  fibrositis,  and  numberless  other 
deviations  from  normal  health.     If  deficient  elimina- 
tion is  treated  in  the  future  from  the  commencement 
— i.e.,  when  the  first  signs  of  metabolic  disturbance 
are  present — by  the  exhibition  of  one  of  the  organic 
extracts   which   regulate   metabolism,   instead   of   by 
occasional   purgation,    we   may   well   hope   that    the 
"  diseases  of  middle  age,  which  arise  during  infancy 
or   adolescence,"   may   no   longer   be   regarded   as    a 
necessary  concomitant  of  advancing  years. 

This,  then,  is  what  we  mean  by  the  statement  that 
our  knowledge  of  organo-therapy  may  conceivably  be 
extended  to  the  avoidance  of  organic  lesions  in  the 
near  future.  We  have  already  pointed  out  that  the 
thyroid,  pituitary,  and  pancreas,  to  mention  three  out 
of  many,  are  intimately  concerned  in  the  control  of 
metabolism,  and  that  a  deficiency  in  secretion  of  either 


336   THE  ORGANS  OF  INTERNAL  SECRETION 

of  the  first  two  glands  results  in  a  storage  of  waste 
products,  in  thickenings  of  the  subcutaneous  tissues, 
and  in  the  retention  of  chemical  substances  which 
should  leave  the  body.  Such  conditions  disappear 
upon  the  administration  of  the  extracts  of  these 
organs. 

By  comparing  these  syndromes  with  that  which 
accompanies,  let  us  say,  "  idiopathic  "  obesity,  or  the 
gouty  diathesis,  we  must  at  once  be  struck  by  the 
similarity  of  the  two  pictures.  Therefore  it  does  not 
seem  to  be  stretching  a  point  to  say  that,  were  these 
latter  diseases  suitably  treated  in  the  early  stages,  it 
would  be  possible  so  to  regulate  metabolism  and  to 
effect  adequate  elimination  that  the  system  would  be 
restored  to  the  status  quo  ante.  The  advanced  stages 
of  faulty  elimination  which  are  now  encountered  in 
the  out-patient  and  consulting- room  could  thereby  be 
avoided. 

This  is,  doubtless,  looking  far  ahead;  but  if  we  are 
justified  in  assuming  that  the  majority  of  the  diseases 
of  middle  age  date  from  childhood,  and  are  in  conse- 
quence incurable,  it  behoves  us  to  look  around  for  a 
means  of  avoiding  such  a  lamentable  state  of  affairs. 

Slight  degrees  of  hypo-endocrinism  usually  recover 
without  aid  from  opo-therapy.  If,  however,  they  do 
not,  it  is  conceivable  that  the  perversion  of  metabolism 
commences  from  such  a  condition,  initiated,  let  us  say, 
by  an  infectious  disease.  The  faulty  elimination  is 
at  first  slight,  but  increases;  the  individual  takes  less 
exercise  as  his  age  advances,  and  when  he  reaches  his 


CONCLUSIONS  337 

fourth  decade,  he  is  probably  prematurely  old,  physi- 
cally unfit,  with  yet  no  defmito  signs  of  organic 
disease.  Nevertheless,  another  ten  years  may  have 
altered  his  condition  for  the  worse:  the  blood-pressure 
may  be  high,  the  urine  show  a  trace  of  albumin  and 
a  decidedly  acid  reaction,  the  joints  be  stiff,  the 
hirsutes  scanty,  and  the  skin  dry  and  its  appendages 
lifeless. 

Every  practitioner  is  farniliar  with  such  a  type — a 
man  aged  at  fifty  !  Even  now  he  will  feel  benefit  in 
many  cases  by  an  organic  remedy.  But  twenty  years 
before  what  a  difference  the  adjustment  of  his  hormone 
balance  would  have  made  to  his  future  health  and 
comfort  ! 

The  present  writer  has  seen  many  ailments,  slight 
in  themselves,  but  of  some  considerable  tenacity,  dis- 
appear upon  the  administration  of  thyroid  extract. 
He  has  also  seen  patients,  who  admit  that  "  there  is 
nothing  wrong  with  them,"  attain  a  degree  of  health 
which  they  had  not  known  for  years  from  the  same 
treatment.  He  is  convinced,  therefore,  that  a  great 
future  lies  in  front  of  organo-therapy;  but  it  must  be 
given  every  chance:  to  wait  until  the  patient's  system 
has  become  altered  by  years  of  faulty  elimination  is  to 
deny  the  rational  remedy  a  fair  chance  of  success. 

This,  then,  is  a  plea  for  the  early  use  of  organic 
extracts  in  every  case  where  their  administration 
appears  to  be  indicated.  By  their  prompt  use  there 
can  be  small  doubt  that  many  derangements  will  be 
righted  before  they  can  become  diseases,  and  it  will 

22 


338   THE  ORGANS  OF  INTERNAL  SECRETION 

not  be  necessary  for  our  successors  in  medical  practice 
to  make  the  lamentable  confession  recorded  by  the 
writer  of  the  article  referred  to  above. 


This  book  has  aimed  at  presenting  to  the  reader 
a  short  survey  of  the  organs  of  internal  secretion,  their 
diseases,  and  the  uses  to  which  preparations  of  the 
hormone-producing  glands,  and  of  organic  tissue 
generally,  may  be  put.  At  the  close  of  this  chapter 
will  be  found  a  short  bibliography,  and  the  reader 
anxious  for  a  fuller  account  of  this  subject  is  referred 
to  the  works  there  mentioned.  Many  of  these  deal 
with  one  gland  only,  while  some  are  general  surveys 
of  organo-therapy. 

Among  the  large  treatises  which  have  been  published 
in  the  last  few  years  is  Cushing's  book  on  the  pituitary 
gland;  Leopold-Levi  and  H.  de  Rothschild's  study  of 
thyroid  deficiency;  and  a  monumental  work  by  Allen 
on  glycosuria  and  diabetes.  In  "  Internal  Secretions 
and  the  Principles  of  Medicine,"  Sajous  has  supplied 
a  work  which  includes  the  study  of  the  internal  secre- 
tions and  the  disorders  which  arise  as  a  result  of  a 
faulty  endocrine  working.  This  author  lays  especial 
stress  upon  the  importance  of  the  suprarenal  secretion, 
and  the  part  it  plays  in  the  bodily  harmony. 

The  study  of  lengthy  and  exhaustive  treatises  such 
as  these  is  often  impossible  for  the  busy  practitioner, 
and  the  present  volume  has  attempted  to  summarize 
the  subject  in  as  brief  a  space  as  is  possible. 

For  those  desirous  of  obtaining  the  latest  informa- 


BIBLIOGRAPHY  389 

tion  which  is  available  on  the  practical  side  of  the 
subject,  Harrower's  book  well  repays  a  careful  perusal. 
Not  only  has  this  author  collected  a  large  amount  of 
literature  dealing  with  the  internal  secretions,  but  he 
has  produced  a  book  which  is  of  really  practical  help 
to  those  desirous  of  prescribing  organic  extracts. 

For  a  histological  survey,  Schafer's  work  entitled 
"  The  Endocrine  Glands  "  should  be  consulted;  while 
Biedl's  book  on  the  "  Internal  Secretory  Organs  "  is  a 
careful  and  thorough  account  of  the  subject  from  all 
standpoints,  although  it  does  not  deal  with  hormone- 
therapy. 

A  list  of  notable  contributions  to  this  subject  is 
appended. 


BIBLIOGRAPHY 

The  Diseases  of  the  Ductless  Glands;  for  Practitioners 
of  Medicine  and  Surgery.  By  S.  P.  Beebe,  Ph.D., 
M.D.  Phil. 

The  Nervous  and  Chemical  Regulators  of  Metabolism. 
By  D.  Noel  Paton,  M.D.,  B.Sc.  Macinillan,  London  and 
New  York. 

Organo-Therapy;  or,  Treatment  by  Means   of  Prepara- 
tions of  Various  Organs.     By  H.   Batty  Shaw,  M.D 
Lond.,  F.R.C.P.     Cassell  and  Co.,  London. 

Glandes  Surrenales  et  Organes  Chromaffines.  By  Lucien 
et  Parisot.     Gittler,  Paris. 


340   THE  OKGANS  OF  INTERNAL  SECEETION 

The  Pituitary  Body  and  its  Disorders.  By  Harvey  Cushing, 
M.D.     Lippincott,  Philadelphia. 

The  Practitioner,  London.  Special  numbers  for  January  and 
February,  1915,  vol.  xciv.,  Nos.  1  and  2. 

Glycosuria  and  Allied  Conditions.  By  P.  J.  Cammidge, 
M.D.  Lond.     Arnold,  London. 

Diseases  of  the  Thyroid  Gland,  By  George  R.  Murray, 
M.A.,  M.D.     Lewis,  London. 

The  Internal  Secretions.  By  E.  Gley.  Translated  by 
M.  Fishberg.     W.  Heinernann. 

New  Aspects  of  Diabetes.  By  Professor  Carl  Von  Noorden, 
Vienna.     Wright,  Bristol. 

The  Endocrine  Organs.  By  E.  A.  Schafer,  Longmans, 
Green  and  Co.,  London. 

Practical  Hormone-Therapy.  By  H.  R.  Harrower,  M.D. 
Bailliere,  Tindall  and  Cox. 

Physiological  Principles  in  Treatment.  By  W.  Langdon 
Brown.     Bailliere,  Tindall  and  Cox. 

Internal  Secretion  and  the  Ductless  Glands.  By  Swale 
Vincent,  M.D.,  D.Sc.     Arnold,  London. 

The  Internal  Secretions  and  the  Principles  of  Medicine. 
By  Charles  de  M.  Sajous,  M.D.,  LL.D.  Davis,  Phila- 
delphia; Phillips,  London. 

The  Internal  Secretory  Organs:  Their  Physiology  and 
Pathology.  By  Professor  Dr.  Arthur  Biedl.  With  an 
Introductory  Preface  by  Leonard  Williams,  M.D.,  M.R.C.P. 
Translated  by  Linda  Forster. 


BIBLIOGEAPHY  341 

The  Thyroid  Gland  in  Health  and  Disease.     By  Robert 
McCarrison.     Bailliere,  Tindall  and  Cox,  London. 

The  Involuntary  Nervous  System.    By  W.  H.  Gaskell,  1920, 
Longmans,  Green  and  Co.,  London. 

Vagotonia:  A  Clinical  Study  in  Vegetative  Neurology 
By  Eppinger  and  Hess.     Translated  by  W.  M.  Kraus  and 
S.  Jelliffe,  New  York. 

Bodily  Changes  in  Pain,  Hunger.  Fear  and  Rage.    By 
Walter  B.  Cannon,     Appleton  and  Co.,  New  York. 

Medical  Diseases  of  the  War.     By  A.  F.  Hurst.     Arnold, 
London. 


WORKS  ON  FUNCTIONAL  NERVOUS  DISEASES. 

Les    Obsessions    et   la   Psychasthenie.     By   Pierre   Janet. 
2  vols.     Alcan,  Paris. 

Psychoneuroses  and  Psychotherapy.     By  Dr.  Dejerine, 

Neurasthenia   or   Nervous    Exhaustion.    By   Dr.    Beard. 
Wood  and  Co.,  New  York,  1880. 

The  Psychology   of  Insanity.     By  Bernard  Hart.    Camb, 
Univ.  Press. 

Functional  Mental  Illnesses.     By  R.  G.  Rows  and  David 
Orr.     Reprinted  from  the  Edinburgh  Medical  Journal,  1920. 

The  Mental  State  of  Hystericals.     By  Pierre  Janet,  M.D. 
Putnam,  New  York. 

Treatment  of  the  Neuroses.     By  Ernest  Jones.     Bailliere, 
Tindall  and  Cox,  1920. 


342    THE  OKGANS  OF  INTEENAL  SECKETION 

The  Psycho-Neuroses  of  War.     By  Roussy  and  L'Hermitte. 
University  of  London  Press. 

Hysteria  or  Pithiatism.     By  J.  Babinski  and  T.  Froment. 
University  of  London  Press. 

Hysterical    Disorders    of    Warfare.     By   Dr.   Yealland. 
Macmillan  and  Co.,  London. 

The  Instinct  of  the  Herd  in  Peace  and  War.    By  W.  Trotter. 
Fisher  Unwin,  London. 

The   Introduction  to  Social  Psychology.      By  Prof.  W. 
McDougall.     Methuen. 


By  Prof.  SIGMUND  FREUD. 

The  Psycho-Pathology  of  Everyday  Life.     Fisher  Unwin, 
London. 


Selected  Papers  on  Hysteria.     The  Journal  of  Nervous  and 
Mental  Disease  Publishing  Co.,  New  York. 

Die   Traumdeutung.     The  Interpretation  of   Dreams.     Allen 
and  Co,  1913. 


By  Dr.  JUNG. 

Analytical  Psychology.     Bailliere,  Tindall  and  Cox,  London 

Psychology  of  the  Unconscious.     Moffat,  Yard  and  Co., 
New  York. 

Theory  of  Psycho- Analysts.     The  Journal  of  Nervous  and 

Mental  Disease,  New  York. 


INDEX 

TAGE3 

Abderhalden,  and  origin  of  dementia  prsecox  . .  . .     270 

,,  tests 


Acro-erythrosis 
Acromegaly   . . 
Addison,  quoted 
Addison's  disease 
Adrenal  glands,  the 


by  . .  . .  . .  270, 271 

99 

. .     135,  136,  137 

..151 

. .      33,  164,  165 

151  et  seq. 

anatomy  and  physiology  of       . .  . .     152 

,,  cortex,  composition  of  . .  154,  155 

,,  effects  of  removal  of    . .  . .  155 

extract  of       ..  ..  290,291,311,323 

,,  functions  of   . .  . .  . .  .  •     157 

,,  insufficiency  of  . .  .  •  162.  163 

,,  medulla  of     . .  . .  . .  152.  153 

,,  therapeutics  of  . .  . .  166,  323 

Adrenalin  . .  . .  . .  . .  . .  •  •      159 

,,         characteristics  of    . .  . .  . .  . .     159 

,,         composition  of       . .  . .  . .  . .     153 

,,  discovery  of  . .  . .  .  .  •  •      153 

,,  effects  of  administration  of  . .  . .  159,  160 

,,  intramuscular  injection  of    ..  ..  160,161 

Aiberti,  quoted         . .  . .  .  •  •  •  •  •     191 

Alpha-iodine  . .  . .  . .  . .  •  •     124 

Amylopsin  . .  . .  . .  . .  •  •     215 

Arnaud,  Francois,  quoted       . .  . .  •  •  . .     156 

Backward  children   . .  . .  . .  145,  324.  325.  326 

,,  treatment  by  pituitary  extract    115.  324-325 

,,  ,,  pluriglandular  extracts. .     327 

,,  ,,  thymus  extract  ..     327 

Bartels,  quoted         . .  . .  . .  . .  • .     138 

Basch,  experiments  with  placental  extract         . .  . .      195 

Basedow's  disease  (see  Graves' Disease)  ..  ..55-56 

Battle-dreams  in  shell-shock  . .  . .  . .  . .     255 

Baumann,  and  thvroid  colloid  . .  . .  41 

Bayiiss  and  Starling,  quoted  . .  . .  19,  24,  175,  213 

Beard,  quoted  . .  . .  . .  . .  •  •     247 

Bernard,  Claude,  quoted         . .  . .  . .  .  .18, 22 

343 


344    THE  ORGANS  OF  INTERNAL  SECRETION 


Berthold 

Bibliography 

Biedl,  quoted  . .  . .  . .  18,  19 

Bile,  therapeutics  of 
Bile-salts,  injections  of 
Blair  Bell,  quoted     . . 

,,  and  calcium  metabolism 

,,  and  osteomalacia   . . 

,,  and  treatment  by  ovarian  extract 

Blepharo-clonus  in  Graves'  disease 
Blood-pressure  in  adrenal  disorders 

,,  use  of  adrenalin  in  raising  the 

Boyle,  and  use  of  splenic  extract 
British  Organo-therapy  Co.,  preparations  of 
Brown-Sequard.  quoted 

Cachexia  strumpriva 

Campbell,  H.,  and  Graves'  dsiease 

Cannon,  quoted 

Cassowary  neck 

Chaiones 

Charcot,  and  hysteria 

Cheadle,  and  Graves'  disease 

Children,  backward 

Chittenden,  quoted 

Choline  glands 

Chromaffin  system    . .  . .  . .     21,  28 

Claude,  Bernard,  quoted 

Cod -liver  oil,  value  of 

Conclusions 

Constipation  in  thyroid  insufficiency 

Cortico-adrenal  virilism,  case  of 

Cushing.  and  hyperpituitarism 

,,         and  hypopituitarism 

,,         and  thyroidectomy  . . 

,,         quoted 

Dale,  quoted 

Darwin,  Charles,  quoted  in  footnote 

Dandy  and  Goetsch,  quoted  . . 

Davidson,  quoted     . . 

Dementia  preecox 

,,  symptoms  of 

,,  theories  of  its  genesi 

Diabetes,  islets  of  Langerhans  in 
;,         relation  to  pancreas 
,,         treatment  of,  by  opo-therapy 


PAGES 

..       18 

..     339 

35,  158-199.  229 

226-312 

81,  294 

169,200.206,207 

..     207 

..     169 

..     208 

..       66 

158.  159 

159.  160 
..  322 
..     289 

18,  22,  291 

39,87 

83 

245,  246,  247.  265 

..     115 

19 

..     249 

..       73 

145,  324.  325.  326 

..       61 


29,  30, 


37 

U 


237 

154 

i.  22 

..     220 

331  et  seq. 

96,  110 

120,  191 

..     142 

..     144 

..       30 

30,  142  et  seq, 

..  50 
..  90 
..  130 
..  145 
267  et  seq. 
267.  268 
..  269 
..  177 
177,  178 
184.  185 


INDEX  345 

PAGES 

Diabetes.  Von  Noorden  and   . .             . .             . .  . .     179 

Digestion,  internal  secretions  of            . .              . .  211  et  seq. 

„          relation  to  spleen  of             . .              . .  . .     228 

Digitalis,  use  of.  in  Graves'  disease     . .              . .  80 

Dreyer,  Ascher,  and  Tschehoksaroff,  and  experiments  in 

dementia  praecox              . .              . .              . .  . .     270 

Dyspituitarism,        . .             . .             . .             . .  . .     138 

case  of         . .             . .             . .  3015  302 

"  Dystrophia  adiposogenitalis  "            . .             . .  . .     138 

Eck's  fistula              . .             . .             . .             . .  . .     218 

Edkins.  and  gastrin                 . .              . .  . .  . .     213 

Eiselberg,  quoted      . .              . .              . .              . .  51 

Electro-therapy        . .              . .              . .  . .  .  .     277 

Elixir  Colloid            . .             . .             . .  . .  . .     289 

,,      Hypophysis   ..             ..             ..  ..  1 47, 289 

Cerebri  ..             ..  ..  ..289 

Elliott.  T.  R.,  quoted  . .  . .  . .     154,  155,  164 

Endocrine  glands,  antagonistic  action  of  . .  . .     281 

Endocrine  glands  and  nervous  disorders  . .  . .     244 

Endogenous  goitre   . .              . .              . .  . .  99 

Entero-kinaise          . .              . .              . .  . .  216.  217 

Eppinger  and  Hess,  and  Graves'  disease  . .  63,  236 

Erdheim,  quoted      . .              . .              . .  . .  65 

Erepsin       . .              . .              . .              . .  . .  . .     217 

Exophthalmic  goitre  (see  Graves'  disease)  . .  . .       55 

Eyebrow  sign  in  thyroid  deficiency       . .  . .  . .  2,  96 

Fallopian  tubes,  after  ovariectomy       . .  . .  . .     196 

Falta,  Eppinger,  and  Rudinger,  and  hyperthyroidism      . .       28 

Fichera,  quoted        . .              . .              . .  . .  . .     197 

Figgis,  Bradley,  and  backward  children  . .  . .     226 

Foa.  quoted               . .              . .              .  .  . .  . .      195 

Freud,  Professor,  quoted         . .              . .  . .  251.  255 

Frohlich,  quoted      . .              . .              . .  . .  138 

Fronime,  quoted       . .              . .              . .  . .  . .     134 

Functional  nervous  disease     . .  . .  . .  244  et  seq. 

Galen  and  Vesalius,  quoted    . .              . .  . .  . .     129 

Gaskell,  and  the  involuntary  nervous  system     . .     235,  236,  238 

Gastric  and  intestinal  secretions           . .  . .  . .     212 

Gastrin       . .             . .              . .              . .  , .  mt     213 

Gatch,  and  hyperthyroidism  . .              . .  . .  66.  67 

Gautrelet,  quoted     . .             . .              . .  . .  . .     237 

Gibson,  and  treatment  of  Graves'  disease  . .  . .     283 

Gilbert  and  Carnot,  quoted    . .              . .  . .  .  .     221 

Gley.  experiments  with  thyroid  extract  . .  . .       49 

Glycogenosis          . .              . .              . .  . .  . .     234 


346    THE  OBGANS  OF  INTERNAL  SECRETION 


in 


Glycosuria 

,,  and  adrenalin 

,,  and  removal  of  pancreas 

Goetsch,  quoted 
Gonads,  the,  extracts  of 

,,  and  nervous  system 

,,  and  relations  to  adrenal  glands 

»»  ,,  parathyroids 

•>  ,,  pituitary 

>>  ,,  thymus  . . 

>>  ,,  thyroid   . . 

Gowing-Middleton.  Dr.,  quoted 
Graafian  follicles 
Graves'  disease 

-,  among  soldiers 

>»  blepharo-clonus  in 

,,  definitions  of 

,,  electrical  resistance  of  skin  in 

,t  etiology 

,,  histological  changes  in  thyroid 

,,  history  of 

,y  indicanuria  in 

, ,  insanity  in 

• ,  mental  changes  in 

,,  prognosis  in  . . 

, ,  treatment  in 

t$  tremor  in 

Gull  and  Ord,  discovery  of  myxcedema  by 

.,  and  hyperthyroidism     . . 

Halban,  and  the  mammarv  gland 
Halliburton.  W.  D.,  quoted 
Hallion,  and  organo-therapv 
Harrower,  H.  R,,  quoted.  134.  165.  166,  167,  180, 

207 
Hedon.  quoted 
Henoch,  quoted 
Hepatic  extract,  use  of.  in  functional  disturbances 

,,        cirrhosis 

, ,       inactivity 
"  Herd  instinct  "      . . 
Herring,  quoted 

Hertoghe,  quoted     . .  . .  105,  106, 

Hertzler,  quoted 
Hormonal 
Hormone -therapy     . . 

,,  practical  points  in  .. 


30 


PAGES 

178  etseq. 
166.  239 
..  183 
66,  143 
..  291 
..     241 

31,  203 

32,  204 

31,  203 

32.  204 
31,  203 

3.  304,  305 

34,  35 

55  et  seq. 

..     265 

..       66 

55.56 

..       68 

..       59 

..       64 

..       56 

75 

70,71 

69,70 

..       72 

73  et  seq. 

..       66 

39.  89 

66,  67 

..     194 
..     176 

..     282 

185.  186.  205, 

.  225.  280.  293 

..     178 

..       59 

of  liver      233 

..     224 

..     224 

..     260 

..     131 

120  etseq.,  285 

..     265 

..     227 

19,37 

315  et  seq. 


INDEX 


347 


PAGES 


Hormone-therapy,  therapeutic  application  of 

280  et  seq. 

.,                 utility  of  empirical  prescribing 

. .     319 

Hormones,  relation  to  nervous  control 

238.  239 

Hormotone 

13 

Horsley,  quoted 

26.  43 

Houssay,  and  treatment  by  adrenal  extract 

..     170 

Hunt,  quoted 

51 

Hurst,  quoted 

47 

Hustin,  quoted 

..     215 

Hyperadrenia,  symptoms  of  . . 

..     172 

Hypergh'csemia 

178.181 

Hyper-oophorism 

..     208 

Hyperpituitarism 

135.  137 

, ,                 treatment  of 

141  et  seq. 

Hyperthyroidism  (see  Graves'  Disease) 

98.  10!  et  seq. 

,,               and  the  neuroses 

..     264 

,,                among  soldiers 

..     265 

Hypo-adrenia 

..     162 

,,           functional 

..     163 

, ,           progressive 

..     163 

, ,           symptoms  of     . . 

163,  165 

, ,           terminal 

..     163 

, ,           treatment  of 

166,  167 

Hypo  -oophorism 

..     209 

Hypophysin 

..      135 

Hypopituitarism 

. .     138 

,,               symptoms  of 

..     138 

,,               treatment  of 

. .      143 

Hypothyroidism  (see  Thyroid  Deficiency) 

87 

,,               associated  with  hyperthyroidism 

..       98 

,,               lesser  degrees  of 

91,92 

,,               treatment  of               ..            123, 

125.  128,  129 

Hysteria     . .              . .              . .              . .                 249  et  seq.,  257 

Indicanuria,  in  Graves'  disease  . .  . .  75 

Internal  secretions,  inter-relation  of  the  ductless  glands  . .       24 

, ,  physiology  of  the  ductless  glands       1 7  et  seq. 

Intestines,  extracts  of  . .  . .  . .    213,  214.  312 

,,  paresis  of  treatment  of         ..  ..  ..     227 


Janet,  Pierre,  quoted 


..    247.240,250 


Kendall,  quoted 

Kinazyme 

Kocher.  and  cachexia  strumpriva 


124 

187 

39 


348   THE  ORGANS  OF  INTERNAL  SECRETION 


Kocher,  quoted         . .             . .             . .  . .  78,  79 

Konigstein,  quoted  . .             . .             . .  . .  . .     195 

Lane,  Sir  W.  Arbuthnot,  quoted           . .  . .  4,  52,  121 

Langerhans,  islets  of               . .             . .  . .  . .     175 

Langlois,  quoted       . .              . .              . .  . .  . .     166 

Leduc .  quoted          . .             . .             . .  . .  . .     208 

Leopold-Levi  and  H.  de  Rothschild,  quoted       . .  96,  98,  338 

Leydig,  cells  of         . .             . .             . .  . .  32,  192,  199 

Lipomatosis,  in  Graves'  disease             . .  . .  68 

Liver,  extracts  of     . .             . .             . .  218,  220,  223,  226,  312 

.,     functions  of    . .             . .             . .  . .  . .     218 

,,     production  of  bile  by    ..             ..  ..  ..     218 

,,     treatment  of  diabetes  by  extracts  of       . .  . .     225 

Lorand,  quoted         . .             . .             . .  . .  29,  31 

Lower,  quoted          . .              . .              . .  . .  .  .      129 

Lowy  and  Richter,  investigations  in  castrated  animals     . .     197 


MacCullum.  and  the  parathyroids 
MacDougall,  and  shell-shock 
Mackenzie,  and  Graves'  disease 
Magnier.  quoted 
Mammar}'  gland 

„  effects  of  castration   .. 

,,  extracts  of  . . 

.,  relation  to  ovary 

,,  ,,        uterus 

Mansfeld,  and  thyroidectomy 
Marie,  quoted 
Marshall  and  Jolly,  quoted 
Mayos,  the,  quoted 
McKennan,  and  epilepsy 
Mental  chorea 

Minskowski,  and  Von  Mering,  and  diabetes 
Mobius,  quoted 
Morris,  quoted 
Mott,  Sir  F..  quoted 
Murray,  G.  R.,  quoted 

Muscular  work,  effects  of  orchitic  extract  on 
Myxcedema 

,,  gait  in   . . 

. ,  Murray's  treatment  of 

. ,  origin  of  name 

pathology  of 

,,  symptoms  of 

Xeo-hormonal 

Xervous  control,  relation  of  hormones  to 


45 
259 

57,  81,  82 

144.  324 

..     194 

..     196 

209,  210,  295 

194,  209,  210 

..     194 

..     240 

..     135 

200.  202 

..       79 

..     139 

..       71 

..     177 

66.  249 

..     179 

..     254 

..       38 

..     291 

88  et  seq . 

. .  89-91 

38,  98 

40.88 

88.  89 

..       90 

227.  228 

238  et  seq. 


40. 


INDEX  349 

PAGES 

Nervous  control,  and  thvroid  secretion  . .  . .     239 

Neurasthenia             ..              ..              ..  10,  161,  247,  248 

,,            traumatic         ..              ..  ..  ..     221 

Nux  vomica,  use  of,  in  Graves'  disease. .  ..  ..       81 

Obesity  in  thyroid  deficiency                 . .  . .  115.  287 

,,        juvenile       ..              ..              ..  ..  ..     317 

Oliver  and  Schafer,  quoted     . .              . .  . .  151.  158,  159 

Oophorectomy          . .              . .              . .  . .  . .     202 

Opie,  and  diabetes   ..              ..              ..  ..  ..177 

Oppenheim,  quoted                 . .              . .  . .  66.  73 

Organo-therapy,  general  survey  of        . .  . .  295,  296 

,.               therapeutic  use  of      ..  ..  298  et  seq. 

Osier,  quoted             . .              . .              . .  . .  57,  166 

Osokin,  quoted         . .              . .              . .  . .  . .     246 

Osteomalacia            . .              . .              . .  . .  46 

,,  and  treatment  by  suprarenal  extract         ..      169 

Ott  and  Scott,  quoted             . .              . .  . .  134 

Ovaries,  effects  of  removal  of                 . .  . .  32,  196,  203 

extracts  of                  . .              .  .  .  .  199,  311 

relation  to  mammary  gland    . .  . .  194,  209,  210 

„           menorrhagia           . .  . .  . .     208 

,,           osteomalacia          . .  . .  . .     198 

therapeutics  of          . .              . .  . .  206,  207 

Pancreas,  the            . .              . .              . .  . .  174  et  seq. 

„         anatomy  and  physiology  of  .  .  174,  175  et  seq, 

,,        origin  of  internal  secretion                   ..  175,176 

,,         relation  to  diabetes  of           ..  ..  ..241 

,,                ,,          nervous  system   . .  . .  178,  179 

,,         secretion,  external  . .              ..  ..  ..     176 

internal..              ..  ..  176,177.182 

,,         therapeutic  use  of  preparations  of      ..  184,  et  seq. 

Paralysis  agitans  and  parathyroid  glands  . .  . .       47 

Parathyroid  glands  . .             . .             . .  . .  45 

and  calcium  metabolism       . .  45,  46 

and  tetany              . .              . .  46,  49 

deficiency                . .  . .  47.  48 

extracts  of              . .  . .  45,  310,  312 

relation  to  nervous  system  . .  . .     240 

structure  of            . .  . .  . .       4.3 

Parenchymatous  goitre           . .              . .  . .  79 

Parotid  juice             . .              . .              . .  . .  . .     212 

Parry,  Caleb,  quoted               . .             . .  . .  56 

Paton,  quoted           . .              . .              . .              . .  31  et  seq. 

Pawlow,  and  succus  entericu-                . .              . .  216,  217 

Peyer's  patches         ..             ..             ..             ..  ..217 


350   THE  OEGANS  OF  INTEENAL   SECEETION 


Pituitary  body,  the  . .             . .             . .  . .             . .     128 

effects  produced  by  disease  of    . .  135  et  seq. 

physiological  functions  of  . .                     132 

pregnancy  cells  in        ..  ..             ..131 

structure  of  . .             . .  . .             . .     129 

test  for  deficient  secretion  of    . .  . .     144 

treatment  of  disorders  of  . .                     140 

by  extracts  of  . .    142,  145,  310 

Pituitrin     ..              ..              ..              ..  ..              ..146 

Pluriglandular  therapy  . .  300,  308,  312,  316,  318,  327 

Post-influenzal  debility            . .              . .  . .              . .         9 

Prael,  quoted            . .             . .             . .  . .                      59 

Pro-gastrin                . .              . .              . .  . .              . .     214 

Progressive  muscular  dystrophy           . .  footnote  to  page  7 

Proptosis.  causation  of,  in  Graves'  disease  . .             . .       65 

Pro-secretin               . .              . .              . .  . .              . .     213 

Prostate,  extract  of                 . .             . .  204, 281,  295,  312 

,,          external  secretion    . .              . .  . .              . .     204 

,,          internal  secretion    . .             . .  . .             . .     204 

Psoriasis,  treatment  with  ovarian  extract  ..             ..     207 

Psychasthenia           . .             . .             . .  . .    247,  249, 250 

Psycho-analysis  in  treatment  of  war  neuroses     . .  . .     275 

Psychological  factors  in  psycho-neuroses  . .             . .     259 

Psycho-neuroses,  the               . .             . .  . .          247  et  seq. 

Psycho-physiological  mechanisms  of  psycho-neuroses       . .     275 

Psycho- therapy         . .             . .             . .  . .          275  et  seq. 

Quinquaud,  quoted  . .              . .              . .  . .                       29 

Rathke's  pouch        . .              . .              . .  . .              . .     130 

Renon  and  Delile,  experiments  of        . .  . .              . .     142 

Reynolds,  and  mental  chorea. .              . .  . .                       71 

Robertson,  Dunlop,  quoted    . .             . .  . .    267,  269,  271 

Robin,  quoted          . .             . .             . .  . .             . .     166 

Sajous.  quoted          . .              . .              . .  22,  32,  156,  319 

Salivary  glands,  secretion  of..              ..  ..             211, 212 

Sandstrom,  quoted    . .             . .             . .  . .                      45 

Sargent,  and  dermatographia                 . .  . .                     163 

. ,       and  hypo-adrenia     . .              . .  . .              ..163 

Schafer,  quoted        . .  . .  19,  20, 139,  177,  178,  185 

Schiff ,  and  removal  of  thyroid  gland    . .  . .                      39 

,,      quoted           ..              ..              ..  ..              ..     319 

Secretin      ..             ..             ..             ..  ..              21,113 

Secretogen                  . .              . .              . .  . .             222,  273 

Serralach  and  Pares,  quoted  . .             . .  . .                     199 

Sertoli's  cells             . .              . .              . .  . .              . .      192 

Sexual  organs,  internal  secretions  of     . .  . .     190,  191,  199 


IXDEX  351 


Sexual  glands,  therapeutics  of 

PAGES 

204,  205 

Shell-shock 

. .  244,  253  et  sea. 

, ,          case  of  . .              . .              footnote  to  page 

203.  204 

, ,          concussion 

, . 

..     244 

, ,          diagram  of 

, . 

..     257 

„          psychological  factors 

, , 

..     259 

, ,          scheme  of 

.  # 

..     257 

. ,          treatment  of 

,  9 

274.  275 

Short,  A.  Rendle,  quoted 

, . 

51,  79 

Souza  and  Castro,  quoted  in  footnote  . . 

, . 

..     193 

Sleep  in  submyxcedema 

. . 

..       97 

Spermin 

. . 

205,  292 

Spleen,  extracts  of    . . 

230. 312 

319,  320 

,,       functions  as  filter  of  . . 

. , 

..     228 

,,       injections  of 

. . 

320,  322 

, ,       inter-relation  to  thyroid 

. . 

..     229 

. ,       in  treatment  of  tuberculosis     . . 

,  . 

..     322 

, ,       relation  to  digestion 

.  9 

..     229 

, ,       removal  of  . . 

, , 

..     229 

Starling,  and  organo-therapy . . 

, . 

..     283 

,,       and  Lane-Claypon,  quoted     .. 

. , 

195.  209 

Steapsin 

. . 

..     215 

Steinach,  experiments  of 

. . 

..     202 

Stelhvag's  sign  in  Graves'  disease 

. . 

62,  66 

Stoddard,  quoted 

. , 

61 

Stokes,  and  Graves'  disease 

,  # 

..       59 

Strophanthus,  use  of,  in  Graves'  disease 

. , 

..       80 

Submyxcedema 

..    92, 

108  et  sea. 

,,               case  of 

footnote  to  page  93 

,,              use  of  thyroid  in 

..    125 

,  126,  333 

Succus  entericus 

..     214 

Swann,  quoted 

, , 

..     170 

Sweating,  absence  of,  in  submyxcedema 

.   , 

116, 117 

Sympathetic  system,  the 

233  et  seq. 

Tachycardia  in  Graves'  disease 

#       # 

78 

Takamine  and  adrenalin 

t       % 

21 

Tandler  and  Gross,  a  case  described  by 

..     197 

Testis,  changes  in  disease  of   . . 

f      f 

..     199 

,,       effects  of  removal  of   . . 

9       # 

196.  197 

, ,       extracts  of    . . 

..     198 

5,204,311 

,,       internal  secretion  of    . . 

191.  192 

,,       undescended,  and  thymus  extract 

..    305,311,327 

Thymus  gland,  and  calcium  metabolism 

, . 

..     308 

,,              extracts  of 

, . 

308.  312 

, ,              and  nervous  system 

. , 

..     240 

,,              and  undescended  testis 

. . 

..     305 

352   THE  ORGANS  OF  INTERNAL  SECRETION 


PAGES 

. .     309 

..       21 

43.  44 

. .     108 

51,  52.  108 

87  et  seq..  103  et  seq. 

106.116 

..     122 


Thymus  gland  use  of,  in  exophthalmic  goitre 
Thy  ro -iodine 

Thyroid;  and  calcium  metabolism 
and  cell  excretion    . . 
antitoxic  function  of 
deficiency  . . 

,,         in  children 

treatment  of  ..  ..     122.124.127 

excess  of    . .              . .             . .  . .  55  et  seq. 

extract  of  . .  124  et  seq.,  285,  287,  307,  320,  337 

,,         combined  with  adrenal  extract  . .     307 

pituitary  . .  288,  302 

functions  of              . .             . .  . .  50 

instability                 . .             . .  . .  98,  99 

results  of  removal  of               . .  . .  42.  43 

secretion,  and  the  sympathetic  nervous  system  . .     239 

weight  of   . .             . .              . .  . .  41 

Trotter.  W.,  and  herd  instinct              . .  . .  . .     260 

Trousseau,  and  Graves'  disease              . .  . .  57.  59 

Trvpsin      ..              ..              ..              ..  ..  ..216 

Trypsogen                 . .             . .             . .  . .  186.  294 

Uterus-  the,  and  mammary  gland         . .  . .  194 

Vassale,  experiments  with  thyroid  extract  . .  26.  39 

Vernet,  administration  of  adrenal  extract  . .  . .      170 

Vieussens  and  Sylvius,  quoted  . .  . .  . .     129 

Vigoroux.    and   electrical   resistance   of   skin  in   Graves' 

disease  . .  . .  . .  . .  67.  68 

Vincent,  Swale,  quoted  . .  . .    138,  160,  239,  264,  270 

Von  Graefe's  sign  in  Graves'  disease      . .  . .  66 

Von  Mering  and  Minskowski.  and  diabetes 
Von  Xoorden,  and  diabetes 

quoted 
Von  Poehl's  "  spermin  " 

Weed,  quoted 

Wells,  quoted 

Wheelon  and  Shipley,  experiments  of  . . 

Williams,  Leonard,  quoted 

Wirsung,  canal  of     . . 

X-ray  in  Graves'  disease 

Zuelzer's  hormone    . . 


..  177 

,  . 

..  179 

.  . 

..  185 

..  292 

#  # 

..  134 

,  . 

..   42 

footnote  to  page  197 

..  13, 

68.  81,  205 

..  175 

87  et  seq. 

. . 

184,  293 

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